Sienna Biopharmaceuticals (SNNAQ) 8-K Other Events

Exhibit 5.1

February 22, 2019	140 Scott Drive
	Menlo Park, California 94025
	Tel: +1.650.328.4600 Fax: +1.650.463.2600
	www.lw.com
	FIRM / AFFILIATE OFFICES
	Beijing	Moscow
	Boston	Munich
	Brussels	New York
	Century City	Orange County
	Chicago	Paris
	Dubai	Riyadh
	Düsseldorf	Rome
	Frankfurt	San Diego
	Hamburg	San Francisco
	Hong Kong	Seoul
	Houston	Shanghai
	London	Silicon Valley
	Los Angeles	Singapore
	Madrid	Tokyo
	Milan	Washington, D.C.

Sienna Biopharmaceuticals

30699 Russell Ranch Road Suite 140

Westlake Village, CA 91362

Re: FormS-3 Registration Statement FileNo. 333-226595

Public Offering of Up to 9,200,000 Shares of Common Stock

of Sienna Biopharmaceuticals, Inc.

Ladies and Gentlemen:

We have acted as special counsel to Sienna Biopharmaceuticals, a Delaware corporation (the “Company”), in connection with the proposed issuance of up to 9,200,000 shares of common stock, $0.0001 par value per share (the “Shares”). The Shares are included in a registration statement on FormS-3 under the Securities Act of 1933, as amended (the “Act”), filed with the Securities and Exchange Commission (the “Commission”) on August 3, 2018 (RegistrationNo. 333-226595) (as amended, the “Registration Statement”), a base prospectus included in the Registration Statement (the “Base Prospectus”) and a prospectus supplement dated February 20, 2019 (together with the Base Prospectus, the “Prospectus”), and an underwriting agreement dated February 20, 2019 among you and the representatives of the several Underwriters named in the underwriting agreement (the “Underwriting Agreement”). This opinion is being furnished in connection with the requirements of Item 601(b)(5) of RegulationS-K under the Act, and no opinion is expressed herein as to any matter pertaining to the contents of the Registration Statement or related Prospectus, other than as expressly stated herein with respect to the issue of the Shares.

As such counsel, we have examined such matters of fact and questions of law as we have considered appropriate for purposes of this letter. With your consent, we have relied upon certificates and other assurances of officers of the Company and others as to factual matters without having independently verified such factual matters. We are opining herein as to the General Corporation Law of the State of Delaware (the “DGCL”), and we express no opinion with respect to any other laws.

February 22, 2019

Page 2

Subject to the foregoing and the other matters set forth herein, it is our opinion that, as of the date hereof, when the Shares shall have been duly registered on the books of the transfer agent and registrar therefor in the name or on behalf of the purchasers and have been issued by the Company against payment therefor in the circumstances contemplated by the Underwriting Agreement, the issue and sale of the Shares will have been duly authorized by all necessary corporate action of the Company, and the Shares will be validly issued, fully paid and nonassessable. In rendering the foregoing opinion, we have assumed that the Company will comply with all applicable notice requirements regarding uncertificated shares provided in the DGCL.

This opinion is for your benefit in connection with the Registration Statement and the Prospectus and may be relied upon by you and by persons entitled to rely upon it pursuant to the applicable provisions of the Act. We consent to your filing this opinion as an exhibit to the Company’s Current Report on Form8-K filed with the Commission on February 22, 2019 and to the reference to our firm in the Prospectus under the heading “Legal Matters.” In giving such consent, we do not thereby admit that we are in the category of persons whose consent is required under Section 7 of the Act or the rules and regulations of the Commission thereunder.

Very truly yours,

/s/ Latham & Watkins LLP