Liver cancer, hepatocellular carcinoma (HCC) in particular, is one of the most deadly cancers worldwide, and the incidence of HCC is increasing rapidly in the United States and other developed countries. Epidemiological studies have identified major risk factors for HCC, including infection with hepatitis B and C virus (HBV and HCV), exposure to certain chemicals, high intake of alcohol, as well as metabolic diseases such as obesity and diabetes that are rapidly rising in the US. Although the etiologies for liver carcinogenesis are relatively well defined, the exact mechanism and pathways leading to cancer development are still unclear. Chronic liver injury, followed by inflammation and irregular liver regeneration has been suggested as an important step in hepatocarcinogenesis. Therefore, the identification of key factors that protect the liver from injury and inflammation could provide valuable insight into the development of HCC. In this review, we will summarize the recent findings in HCC studies, mainly focusing on the new molecular link among inflammation, liver repair and HCC.