Hepatitis B virus (HBV)-human DNA integration is a commonly seen event in the evolutionary process of hepatocellular carcinoma (HCC). HBV chronic infection induces HBV mutation, HBV integration and the inflammatory microenvironment alternation in the hosts, which provides a evolutionary soil for the hepatocarcinogenesis. The second generation sequencing technique provides a better approach for understanding the HBV integration mechanism in HCC. This review focuses on the features of HBV integration and influences of HBV integration on human, virus genomes, and discusses the association of HBV integration with HCC.