Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). In the process from chronic HBV infection to the development of HCC, there is a phenomenon of co-evolution of hepatocytes and HBV. The evolution of hepatocytes includes dedifferentiation and reverse evolution, while the evolution of HBV is mainly "telemorphosis" . Since HBV evolution occurs earlier than the development of HCC, the interaction between them is mainly reflected in the promotion of HCC evolution by HBV mutation. This article briefly summarizes the novel theory termed as cancer evolution and development and elucidates the molecular mechanism of HCC caused by HBV from the perspective of evolution.