Abstract： It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging malignancies of worldwide importance. HCC is a disease that requires multidisciplinary management. There has been no widely accepted standardard systemic therapy for this disease until recently. However, with the arrival of newly developed, molecularly targeted agents, there has been renewed interest in developing novel systemic therapy in HCC. For this review, the authors concisely summarized the current status of molecular targeted agents: muhikinase inhibitor, antiangiogenesis and anti-EGFR agents, which are under clinical development, focus on new agents with promise, particularly sorafenib, a drug that appear to be the new standard of care for advanced HCC.