Abstract: Hepatocellular carcinoma is one of the most commonly occurring malignant tumors. The incidence of hepa-tocellular carcinoma is related with many factors, of which infection of hepatitis-B virus (HBV) is a key factor. This infection has already become a major worldwide problem, but the process leading to liver cancer remains unclear. The long-term car-rying HBV has a significant relationship with the occurrence of hepatocellular carcinoma. HBV greatly promotes the devel -opment of hepatocellular carcinoma resulting from chronic hepatitis, but its specific mechanism of carcinogenesis is still controversial. Hypermethylation of the tumor suppressor gene was found to play an important role in the incidence, devel-opment and metastasis of the HBV- associated hepatocellular carcinoma. The hypermethylation of the tumor suppressor gene has an obvious specificity: it is closely related to the hepatitis B viral infection, and is maintained by DNA methyl-trans-ferase 1. This phenomenon supplies new methods for diagnosis and treatment of the HBV-associated hepatocellular carci -noma. For early diagnosis, risk assessment and preventive treatment of the carcinoma, further discovery and understand-ing of the molecular mechanisms of HBV leading to the hepatocellular carcinoma is extremely necessary. Methylation of tu -mor suppressor gene can be used for early diagnosis of HBV-associated hepatocellular carcinoma. Hypermethylation of tu-mor suppressor gene silencing, by drugs which re-express the antioncogene, may become a research direction in the fu-ture.