As filed with the Securities and Exchange Commission on July 9, 2012

Registration No. 333-            

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM S-8

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

GALENA BIOPHARMA, INC.

(Exact name of registrant as specified in its charter)

310 N. State Street, Suite 208

Lake Oswego, Oregon 97034

(Address of principal executive offices)

Galena Biopharma, Inc. Employee Stock Purchase Plan

(Full title of the plan)

Mark J. Ahn, Ph.D.

President and Chief Executive Officer

Galena Biopharma, Inc.

310 N. State Street, Suite 208

Lake Oswego, Oregon 97034

(Name and address of agent for service)

(855) 855-4253

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

Copy to:

Dale E. Short

Darren T. Freedman

TroyGould PC

1801 Century Park East, Suite 1600

Los Angeles, California 90067

(310) 553-4441

Indicate by check mark (ü) whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act. (Check one):

CALCULATION OF REGISTRATION FEE

EXPLANATORY NOTE

This Registration Statement is filed pursuant to General Instruction E to Form S-8 by Galena Biopharma, Inc., a Delaware corporation (the “Company”), to register 750,000 shares of common stock of the Company in addition to those previously registered on the Company’s Registration Statement on Form S-8 (File No. 333-174819) filed with the Securities and Exchange Commission on June 10, 2011 for issuance pursuant to the Company’s Employee Stock Purchase Plan. Pursuant to General Instruction E to Form S-8, this Registration Statement incorporates by reference the contents of such previously filed Registration Statement.

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PART II

INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

The validity of the shares being registered hereby has been passed upon by TroyGould PC. As of the date of its opinion, that firm owned 123,491 shares of common stock of the Company.

The following exhibits are filed with or incorporated by reference as a part of this registration statement:

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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 Lake Oswego, State of Oregon, on July 9, 2012.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Mark J. Ahn, Ph.D., as his true and lawful attorney-in-fact and agent, with full power of substitution, for him and in his name, place and stead, in any and all capacities, to sign any and all amendments (including post-effective amendments) to this registration statement on Form S-8, with all exhibits thereto and all documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorney-in-fact and agent full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorney-in-fact and agent, or his substitute or substitutes, may lawfully 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:

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EXHIBIT INDEX

The following exhibits are filed with this registration statement or are incorporated by reference as a part of this registration statement: