As filed with the U.S. Securities and Exchange Commission on August 28, 2025

Registration No. 333-

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, DC 20549

FORM S-8

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

Cardiff Oncology, Inc.

(Exact name of registrant as specified in its charter)

11055 Flintkote Avenue

San Diego, CA 92121

(858) 952-7570

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Cardiff Oncology, Inc. Employee Stock Option Agreements

2021 Omnibus Equity Incentive Plan

(Full title of the plan)

Mark Erlander, Ph.D.

Chief Executive Officer

Cardiff Oncology, Inc.

11055 Flintkote Avenue

San Diego, CA 92121

(858) 952-7570

(Name and address of agent for service)

(858) 952-7570

(Telephone number, including area code, of agent for service)

With copies to:

Jeffrey J. Fessler, Esq.

Sheppard, Mullin, Richter & Hampton LLP

30 Rockefeller Plaza, 39th Floor

New York, New York 10112

(212) 653-8700

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and "emerging growth company" in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of Securities Act. o

TABLE OF CONTENTS

EXPLANATORY NOTE

This Registration Statement is being filed for the purpose of registering an aggregate of 4,635,040 shares of the Registrant’s Common Stock, which includes (i) 635,040 shares of the Registrant’s Common Stock issuable upon the vesting and exercise of stock options granted as inducement awards by the Registrant to employees in accordance with Nasdaq Listing Rule 5635(c)(4), and (ii) an additional 4,000,000 shares of Common Stock that were reserved for issuance under the 2021 Omnibus Incentive Plan. The Registrant previously filed with the Securities and Exchange Commission (the “Commission”) registration statements on Form S-8 on June 10, 2021 (Registration No. 333-256978), July 12, 2022 (Registration No. 333-266103), and on July 1, 2024, registering shares of Common Stock issuable under the 2021 Omnibus Incentive Plan (each, a “Prior Registration Statement,” and together, the “Prior Registration Statements”). This Registration Statement relates to securities of the same class as those to which the Prior Registration Statements relate and is submitted in accordance with General Instruction E of Form S-8 regarding Registration of Additional Securities. Pursuant to General Instruction E of Form S-8, the contents of the Prior Registration Statements are incorporated herein by reference and made part of this Registration Statement, except for Items 3 and 8, which are being updated by this Registration Statement.

PART I

INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS

The documents containing the information specified in Part I of Form S-8 will be sent or given to participants as specified by Rule 428(b)(1) of the Securities Act of 1933, as amended (the “Securities Act”). These documents and the documents incorporated by reference into this Registration Statement pursuant to Item 3 of Part II of this Registration Statement, taken together, constitute a prospectus that meets the requirements of Section 10(a) of the Securities Act.

PART II

INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 3. Incorporation of Documents by Reference

The following documents, which have been filed by the Company with the Securities and Exchange Commission (the “SEC”), are hereby incorporated by reference in this Registration Statement:

All documents subsequently filed by the Company pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act, after the date of this Registration Statement and prior to the filing of a post-effective amendment to this Registration Statement which indicates that all securities offered hereby have been sold or which deregisters all securities then remaining unsold, shall be deemed to be incorporated by reference in this Registration Statement and to be a part hereof from the date of filing of such documents. Any statement contained in a document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded for purposes of this Registration Statement to the extent that a statement contained herein or in any other subsequently filed document which also is or is deemed to be incorporated by reference herein modifies or supersedes such statement. Any such statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this Registration Statement. Copies of these documents are not required to be filed with this Registration Statement, and nothing in this Registration Statement shall be deemed to incorporate information furnished but not filed with the SEC.

Section 145(a) of the Delaware General Corporation Law (“DGCL”) provides, in general, that a corporation may indemnify any person who was or is a party to or is threatened to be made a party to any threatened, pending or completed action, suit or proceeding, whether civil, criminal, administrative or investigative (other than an action by or in the right of the corporation), because he or she is or was a director, officer, employee or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise, against expenses (including attorneys’ fees), judgments, fines and amounts paid in settlement actually and reasonably incurred by the person in connection with such action, suit or proceeding, if he or she acted in good faith and in a manner he or she reasonably believed to be in or not opposed to the best interests of the corporation and, with respect to any criminal action or proceeding, had no reasonable cause to believe his or her conduct was unlawful.

Section 145(b) of the DGCL provides, in general, that a corporation may indemnify any person who was or is a party or is threatened to be made a party to any threatened, pending or completed action or suit by or in the right of the corporation to procure a judgment in its favor because the person is or was a director, officer, employee or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise, against expenses (including attorneys’ fees) actually and reasonably incurred by the person in connection with the defense or settlement of such action or suit if he or she acted in good faith and in a manner he or she reasonably believed to be in or not opposed to the best interests of the corporation, except that no indemnification shall be made with respect to any claim, issue or matter as to which he or she shall have been adjudged to be liable to the corporation unless and only to the extent that the Court of Chancery or other adjudicating court determines that, despite the adjudication of liability but in view of all of the circumstances of the case, he or she is fairly and reasonably entitled to indemnity for such expenses that the Court of Chancery or other adjudicating court shall deem proper.

Section 145(g) of the DGCL provides, in general, that a corporation may purchase and maintain insurance on behalf of any person who is or was a director, officer, employee or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise against any liability asserted against such person and incurred by such person in any such capacity, or arising out of his or her status as such, whether or not the corporation would have the power to indemnify the person against such liability under Section 145 of the DGCL.

Additionally, our Amended and Restated Certificate of Incorporation, as amended, eliminates our directors’ liability to the fullest extent permitted under the DGCL. The DGCL provides that directors of a corporation will not be personally liable for monetary damages for breach of their fiduciary duties as directors, except for liability:

If the DGCL is amended to authorize corporate action further eliminating or limiting the personal liability of directors, then the liability of the Company’s directors will be eliminated or limited to the fullest extent permitted by the DGCL, as so amended.

In addition, we have entered into separate indemnification agreements with our directors and officers. These agreements, among other things, require us to indemnify our directors and officers for certain expenses, including attorneys’ fees, judgments, fines, and settlement amounts incurred by a director or officer in any action or proceeding arising out of their services as one of our directors or officers or any other company or enterprise to which the person provides services at our request.

We maintain a directors’ and officers’ insurance policy pursuant to which our directors and officers are insured against liability for actions taken in their capacities as directors and officers.

For a list of exhibits, see the Exhibit Index in this Registration Statement, which is incorporated into this Item by reference.

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the city of San Diego, State of California, on August 28, 2025.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Mark Erlander as his or her attorney-in-fact, with full power of substitution for him or her in any and all capacities, to sign any amendments to this Registration Statement, including any and all pre-effective and post-effective amendments and to file such amendments thereto, with exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, hereby ratifying and confirming all that said attorney-in-fact, or his substitute or substitutes, may do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, this registration statement has been signed by the following persons in the capacities and on the dates indicated.

EXHIBIT INDEX

* Filed herewith.

August 28, 2025

VIA ELECTRONIC MAIL ONLY

Cardiff Oncology, Inc.

11055 Flintkote Avenue

San Diego, CA 92121

Ladies and Gentlemen:

You have requested our opinion with respect to certain matters in connection with the filing by Cardiff Oncology, Inc., a Delaware corporation (the “Company”), of a Registration Statement on Form S-8 (the “Registration Statement”) under the Securities Act of 1933, as amended, with the Securities and Exchange Commission, covering an aggregate of 4,635,040 shares of the Company’s common stock, par value $0.0001 per share (the “Common Stock”), which includes (i) 635,040 shares of the Registrant’s Common Stock issuable upon the vesting and exercise of stock options granted as inducement awards by the Registrant to employees in accordance with Nasdaq Listing Rule 5635(c)(4) (the “Inducement Shares”), and (ii) an additional 4,000,000 shares (the “Plan Shares” and together with the Inducement Shares, the “Shares”), which may be issued pursuant to the Company’s 2021 Equity Incentive Plan, as amended (the “Plan”).

This Opinion is being furnished in accordance with the requirements of Item 8 of Form S-8 and Item 601(b)(5)(i) of Regulation S-K.

In connection with this opinion, we have reviewed and relied upon the Registration Statement, the Company’s Amended and Restated Certificate of Incorporation, as amended, as in effect on the date hereof, the Company’s Bylaws effective as in effect on the date hereof (the “Bylaws”), the proceedings taken by the Company with respect to the authorization and adoption of the Plan, resolutions adopted by the board of directors of the Company, and such other documents, records, certificates, memoranda and other instruments as we deem necessary as a basis for this opinion. With respect to the foregoing documents, we have assumed the genuineness of all signatures, the authenticity of all documents submitted to us as originals and the conformity to original of all documents submitted to us as certified or reproduced copies. We have also assumed that the Shares will be uncertificated in accordance with Section 158 of the Delaware General Corporation Law, and the transfer agent therefor will register the purchaser thereof as the registered owner of any uncertificated Shares on its stock transfer books and records. We have further assumed that (a) shares of the Common Stock currently reserved for issuance under the Plan will remain available for the issuance of the Shares, and (b) neither the Company’s charter documents nor any of the proceedings relating to either the Plan or any of the award agreements

relating to the Shares will be rescinded, amended or otherwise modified prior to the issuance of the Shares. We have also obtained from public officials and officers of the Company certificates or comparable documents as to certain factual matters and, insofar as this opinion is based on matters of fact, we have relied on such certificates and comparable documents without independent investigation. We have made such other investigations as we have deemed relevant and necessary in connection with the opinions hereinafter set forth.

On the basis of the foregoing, and in reliance thereon, we are of the opinion that the Shares, when issued and sold in the manner referred to in the Plan against proper payment and consideration thereof and pursuant to the agreements that accompany the Plan, will be legally and validly issued, fully paid and nonassessable.

We consent to the filing of this opinion letter as Exhibit 5.1 to the Registration Statement. In giving such consent, we do not thereby admit that we are included in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations of the Securities and Exchange Commission promulgated thereunder.

We express no opinion as to matters governed by any laws other than the Delaware General Corporation Law and reported decisions of the Delaware courts interpreting such law.

This opinion letter is rendered as of the date first written above, and we disclaim any obligation to advise you of facts, circumstances, events or developments which hereafter may be brought to our attention and which may alter, affect or modify the opinion expressed herein. Our opinion is expressly limited to the matters set forth above, and we render no opinion, whether by implication or otherwise, as to any other matters relating to the Company, the Shares, the Plan, the award agreements related to the Shares or the Registration Statement.

Respectfully Submitted,

/s/ Sheppard, Mullin, Richter & Hampton LLP

SHEPPARD, MULLIN, RICHTER & HAMPTON LLP

Consent of Independent Registered Public Accounting Firm

We hereby consent to the incorporation by reference in this Registration Statement of our report dated February 27, 2025, relating to the financial statements of Cardiff Oncology, Inc. (the “Company”) appearing in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024.

/s/ BDO USA, P.C.

San Diego, California

August 28, 2025

CARDIFF ONCOLOGY, INC.

STOCK OPTION GRANT AGREEMENT

FOR NONSTATUTORY STOCK OPTIONS

Cardiff Oncology, Inc., a Delaware corporation (the “Company”) does hereby grant to Guobao Zhang (the “Optionee”), an option (the “Option”) that is NOT intended to qualify as an incentive stock option pursuant to Section 422(b) of the Internal Revenue Code, to purchase shares of the Company’s common stock (“Stock”) in the number and subject to terms and conditions of this Stock Option Grant Agreement (the “Grant Agreement”). The following are the general terms of the Option for shares of Stock (“Option Shares”) granted to Optionee by this Grant Agreement.

The grant date of the Option (“Grant Date”) is April 14, 2025

The number of Option Shares granted to Optionee is 35,040 shares of Stock.

The exercise price (“Exercise Price”) at which Optionee can purchase Option Shares is $2.79 per share.

This Option is not immediately exercisable.

The first day that Option Shares commence to vest is April 14, 2025 (“Vesting Commencement Date”).

Option Shares shall vest in accordance with the following schedule (“Vesting Schedule”):

8,760 of the Options vest on April 14, 2026 and 730 vest monthly for 36 months beginning on May 14, 2026, provided the Optionee on the vesting date continues to provide services to the Company or an Affiliate.

The Option shall expire, and be of no further force or effect, on the tenth anniversary of the Grant Date; provided, however, the Option shall expire within (i) ninety (90) days of termination of service in the event Optionee’s service with the Company or its Affiliates is terminated for any reason other than for Cause or because of Disability or death or (ii) six (6) months following the date of Optionee’s termination of employment with the Company or its Affiliates due to the Optionee’s death or Disability.

The entire Option (vested or unvested) held by the Optionee immediately prior to the termination of Optionee’s employment shall immediately terminate upon such termination of employment if such termination of employment was for Cause.

This option may be exercised by delivering to the Secretary of the Company (i) a written Notice of Intention to Exercise in the form attached hereto as Exhibit A signed by the Optionee and specifying the number of Optioned Shares he desires to purchase,

(ii) payment in full of the exercise price for all such Optioned Shares in cash, certified check or surrender of shares of Common Stock of the Company having a value equal to the exercise price of the Optioned Shares as to which Optionee is exercising this Option, provided that such surrendered shares, if previously acquired by exercise of a Company stock option, have been held by Optionee at least six months prior to their surrender. As a holder of an option, Optionee shall have the rights of a shareholder with respect to the Optioned Shares only after they shall have been issued to Optionee upon the exercise of this option. Subject to the terms and provisions of this Agreement, the Company shall use its best efforts to cause the Optioned Shares to be issued as promptly as practicable after receipt of the Notice of Intention to Exercise.

This Option shall not be transferable and may be exercised during Optionee’s lifetime only by Optionee. Any purported transfer or assignment of this option shall be void and of no effect, and shall give the Company the right to terminate this option as of the date of such purported transfer or assignment. No transfer of an option by Optionee by will or by the laws of descent and distribution shall be effective unless the Company have been furnished with written notice thereof, and such other evidence as the Board of Directors may deem necessary to establish the validity of the transfer and conditions of the option, and to establish compliance with any laws or regulations pertaining thereto

The Optionee hereby accepts this Option subject to all of the terms and provisions thereof. The Optionee hereby agrees to accept as binding, conclusive and final all decisions or interpretations of the Board of Directors upon any questions arising under the Option.

SCHEDULE A

The Optionee may not exercise any of the vested Option Shares more than 90 days after the first date on which he or she ceases to provide services to the Company or a Subsidiary.

In the event of Change of Control (as defined in the Plan), all of the Option Shares will vest and become immediately exercisable.

CARDIFF ONCOLOGY, INC.

STOCK OPTION GRANT AGREEMENT

FOR NONSTATUTORY STOCK OPTIONS

Cardiff Oncology, Inc., a Delaware corporation (the “Company”) does hereby grant to Roger Sidhu (the “Optionee”), an option (the “Option”) that is NOT intended to qualify as an incentive stock option pursuant to Section 422(b) of the Internal Revenue Code, to purchase shares of the Company’s common stock (“Stock”) in the number and subject to terms and conditions of this Stock Option Grant Agreement (the “Grant Agreement”) and the Company’s 2021 Omnibus Equity Incentive Plan (the “Plan”). The provisions of the Plan are incorporated herein by reference, and copies of the Plan have been given to Optionee. The following are the general terms of the Option for shares of Stock (“Option Shares”) granted to Optionee by this Grant Agreement.

The grant date of the Option (“Grant Date”) is June 16, 2025

The number of Option Shares granted to Optionee is 600,000 shares of Stock.

The exercise price (“Exercise Price”) at which Optionee can purchase Option Shares is $3.86 per share.

This Option is not immediately exercisable.

The first day that Option Shares commence to vest is June 16, 2025 (“Vesting Commencement Date”).

Option Shares shall vest in accordance with the following schedule (“Vesting Schedule”):

150,000 vest on June 16, 2026 and 12,500 vest monthly for 36 months thereafter, provided the Optionee on each vesting date continues to provide services to the Company or a Subsidiary.

The Option shall expire, and be of no further force or effect, on the tenth anniversary of the Grant Date; provided, however, the Option shall expire within 90 days of termination of service or in accordance with Section 6 of the Plan in the event Optionee’s service with the Company or a Subsidiary is terminated because of Disability or death.

Net Exercise is available to Optionee.

Special Provisions are set forth on Schedule A hereto.

The Optionee represents that he/she is familiar with the terms and provisions of the Plan, and hereby accepts this Option subject to all of the terms and provisions thereof. The Optionee hereby agrees to accept as binding, conclusive and final all decisions or interpretations of the Board

upon any questions arising under the Option. The Optionee acknowledges receipt of a copy of the Plan.

SCHEDULE A

The Optionee may not exercise any of the vested Option Shares more than 90 days after the first date on which he or she ceases to provide services to the Company or a Subsidiary.

In the event of Change of Control (as defined in the Plan), all of the Option Shares will vest and become immediately exercisable.