Molecular-targeted therapy is a new method and tendency in the treatment of hepatocellular carcinoma (HCC). To date, sorafinib, a multi-targeted gent, is the only one proved to be effective in improving the survival of patients with advanced HCC. Sorafinib is also the first line systemic agent for advanced HCC. Other multi-targeted agents, such as sunitinib, are also proved to be effective. Erlotinib, gefitinib and eetuximab, which target epidermal growth factor receptor, show effectiveness but still need further investigation. Bevacizumab, which targets vascular endothelial growth factor and vascular endothelial growth factor receptor, shows excellent results and deserves more clinical trials. The effects of bortezomib, sirolimus and imatinib, which target other pathways, are still under investigation. The future studies of molecular-targeted therapy for HCC should be focused on the combination of different targeted medicine, and combination of molecular-targeted therapy and chemotherapy, as well as individualized therapy.