The success of the SHARP and Asia-Pacific studies marked a new era of molecular targeted therapy for hepatocellular carcinoma (HCC). Since the approval of sorafenib as a first-line treatment for advanced liver cancer by the Food and Drug Administration (FDA) in 2008, more and more advanced liver cancer patients have benefited from sorafenib treatment. In the following decade, a large number of clinical trials had been conducted to explore more effective drugs and treatments. However, none of these trials were able to find a more effective drug than sorafenib. Regorafenib, cabozantinib, ramucirumab, and sunitinib can be used as second-line treatments when sorafenib is intolerable or when the disease progresses after sorafenib treatment. Lenvatinib was shown to be non-inferior to sorafenib in the 2018 REFLECT study and was hence approved by the FDA as a first-line treatment for HCC.