Hepatocellular carcinoma (HCC), the second cause of cancer-related death in mainland China, is mainly caused by chronic hepatitis B virus (HBV) infection. Genetic predisposition of human leukocyte antigen classⅡ contributes to the maintenance of chronic HBV infection. Nonresolving inflammation resulted from the interaction of HBV and immune system is essential for the evolution of HBV and subsequent HCC occurrence. Persistent and insufficient antiviral immunity positively selects HBV mutants. During the inflammation-promoting carcinogenesis, genome of both HBV and hepatocyte experiences an evolutionary process of "mutation- selection-adaptation". HBV mutations not only predict but also promote the occurrence of HCC. The integration of HBV genome, especially in a form of the carboxylic-terminal truncated HBV X protein, not only promotes HCC occurrence and metastasis, but also confers the resistance to antiviral treatments. Understanding the mechanisms by which HBV induces hepatocarcinogenesis will lay the foundations for decreasing and postponing HCC occurrence and metastasis in the HBV-infected subjects.