This randomized, placebo-controlled, multicenter study will evaluate the efficacy and safety of GC33 (RO5137382) in previously treated patients with unresectable advanced or metastatic hepatocellular carcinoma. Participants will be stratified according to the level of GPC-3 expression in tumors and randomized to receive either GC33 (1600 mg intravenously) or placebo on Days 1 and 8 of Cycle 1 and every 2 weeks thereafter. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically confirmed hepatocellular carcinoma (without fibro-lamellar subtype)
• Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or documented adverse event(s) associated with prior systemic agent(s) that resulted in discontinuance of that (those) agent(s)
• Not a candidate for curative treatments (e.g. resection, transplantation)
• Child-Pugh A (score of 5-6)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate hematologic, hepatic and renal function
• Ability to provide, for central review, a tumor tissue sample to determine the level of GPC-3 expression by IHC
• Measurable disease by RECIST criteria

Exclusion Criteria:

• Child Pugh B or C
• Known hepatocellular carcinoma with fibro-lamellar histology
• Known brain or leptomeningeal metastases
• Active infectious diseases requiring treatment except for hepatitis B and C
• History of organ allograft including liver transplant
• Anticipated or ongoing administration of anticancer therapies other than those administered in this study
• Anticancer treatment within 2 weeks prior to entering the study
• Patients who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies
• Patients receiving interferon therapy
• Pregnant or lactating women
• Known HIV positivity or AIDS-related illness
• History of significant hypersensitivity to similar agents (monoclonal antibody, protein-included drugs, Chinese hamster ovary products)