Chronic hepatitis B virus (HBV) infection has long been the most common cause of hepatocellular carcinoma(HCC). However, some aspects of the pathogenesis of HBV infection and genesis of hepatitis B virus (HBV)-relatedhepatocellular carcinoma (HCC) are still inconclusive. An increasing number of published studies indicate thathepatitis B virus mutations are associated with risk of HCC. These variations include, in particular, mutationsin ORF S,C,X gene regions. This mini-review summarizes results of clinical studies and molecular mechanismson the possible relations of HBV mutations with the development of hepatocellular carcinoma.