Hepatocellular carcinoma (HCC) is the most common primary liver cancer and accounts for 80%-90% of this class of malignancy. So far, understanding of its pathogenesis and effective therapeutic methods are rather limited. In this issue, 11 invited review articles are published to address current advance of underlying molecular mechanisms for the development of HCC, and novel therapeutic approaches for HCC. This series of review articles provide an in-depth unders-tanding of HCC that has led to or may lead to the development of novel therapies for HCC.