There is no effective systemic therapy for patients with advanced hepatocellular carcinoma (HCC) except liver transplantation. Sorafenib, a multikinase inhibitor, has been shown to significantly increase overall survival (OS) in a randomized, placebo-controlled, phase III trial of patients with HCC (SHARP). The aim of this study was to evaluate the effectiveness of sorafenib for advanced HCC by carrying out a meta-analysis of randomized controlled trials that compared sorafenib-based therapy with other agent-based therapy. Randomized controlled trials comparing sorafenib or combined chemotherapy with placebo or combined chemotherapy in advanced HCC between 2000 and 2008 were identified and the data were extracted from reports. Outcomes analyzed were objective response rate, time to progression (TTP), OS, and toxicity. The summary hazard ratios (HRs), odds ratios, and their 95% confidence intervals (CIs) for mortality, objective response rate, and toxicity were estimated. All statistical tests were two-sided. Three trials including 924 patients were identified. Sorafenib-based chemotherapy was also associated with a 79% prolongation of TPP (HR = 0.58, 95% CI = 0.49-0.69, P<0.001), and a 37.3% increase in OS (HR = 0.66, 95% CI = 0.55-0.78, P<0.001). Despite significant increases in the frequencies of hand-foot syndrome and diarrhea in patients receiving sorafenib-containing chemotherapy, no significant difference in other toxic events was observed. This meta-analysis suggests that sorafenib-based chemotherapy is superior to placebo-based chemotherapy in terms of TPP and OS without increase in severe toxic effects.