Regorafenib (Stivarga), a small molecule inhibitor of multiple kinases, is the first drug to be approved for the treatment of hepatocellular carcinoma (HCC) in patients who have progressed during or after sorafenib therapy. Its approval was based on the results of the randomized, double-blind, placebo-controlled, multinational, phase III RESORCE trial in patients with HCC who had progressed during sorafenib therapy. In RESORCE, regorafenib significantly prolonged overall survival (OS; primary endpoint), progression-free survival (PFS) and time to progression (TTP) compared with placebo, with the OS benefit appearing to be largely due to disease stabilization. Regorafenib had an acceptable tolerability profile. The most common treatment-related adverse events in the regorafenib group included hand-foot skin reaction, fatigue, diarrhoea and hypertension. No fatal hepatic failure was reported with regorafenib in patients with HCC in RESORCE. In conclusion, current evidence suggests that regorafenib is an important new targeted therapy option for the treatment of HCC patients who have progressed on sorafenib therapy.