The purpose was to assess the cost-effectiveness of sorafenib in the treatment of hepatocellular carcinoma (HCC) patients incorporating current prices and the results of the recent published field practice SOraFenib Italian Assessment (SOFIA) study. We created a Markov Decision Model to evaluate, in a hypothetical cohort of Caucasian male patients, aged 67 years with Barcelona Clinic Liver Cancer (BCLC) C HCC, or BCLC B HCC who were unfit or failed to respond to locoregional therapies, well compensated cirrhosis, and with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG), the cost-effectiveness of the following strategies: (1) full or dose-adjusted sorafenib for BCLC B and C patients together; (2) full or dose-adjusted sorafenib for BCLC B patients; (3) full or dose-adjusted sorafenib for BCLC C patients. Outcomes include quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). In the base-case analysis dose-adjusted sorafenib was the most effective of the evaluated strategies. For dose-adjusted sorafenib, QALY was 0.44 for BCLC B and C patients together, 0.44 for BCLC C patients, and 0.38 for BCLC B patients. The ICER of dose-adjusted sorafenib compared with BSC was €34,534 per QALY gained for BCLC B and C patients together, €27,916 per QALY gained for BCLC C patients, and €54,881 per QALY gained for BCLC B patients. Results were sensitive to BSC survival rate, and sorafenib treatment duration. Conclusion: In daily practice dose-adjusted, but not full-dose, sorafenib is a cost-effective treatment compared to BSC in intermediate and advanced HCC. (HEPATOLOGY 2013).