Chronic infection of hepatitis B virus (HBV) is the main cause of hepatocellular carcinoma (HCC) in China. Anti-HBV treatment is the key to hepatitis B treatment, which can reduce the risk of HCC, but with unknown mechanism. During chronic inflammation, HBV can evolve into mutants with advantages for survival and carcinogenesis through "mutation-selection-adaption" under the stress of microenvironment in the organism. Therefore anti-HBV treatment to block the process of evolution is critical to prevent carcinogenesis. However, the current anti-HBV treatment may not give full play to cancer prevention due to the limitations of current antiviral agents and standard of treatment, which can partly explain some unexpected findings in clinical research. Based on the characteristics of the HBV-HCC evolution process, cancer prevention can be further improved by enhancing the specificity and rationality of antiviral treatment.