Chronic Hepatitis B Virus (HBV) infection has been identified as a leading risk factor for hepatocellular carcinoma (HCC).It has been estimated that about 53% of HCC cases in the world are related to HBV and almost all of the HBV-associated HCCs harbor chromosomally integrated HBV DNA.Clinical studies show that more than one-third of HBV-integrates in HBV related HCC might encode functional c-terminally truncated middle surface protein of hepatitis B virus (MHBst) transactivators.Functional MHBst transactivators can be generated by deletion of 3sequences of the preS2/S gene and preS2 domain has been considered as the minimal functional unit.The preS2 activators can activate transcription factors like AP-1 and NF-κB via PKC-dependent activation of the c-Raf-1/MAP2-kinase signaling cascade.An increased incidence of liver tumor has been found in MHBst transgenic mice older than 15 months which indicates the important role of preS2 transactivator in tumorogenesis.however, the detail mechanism remains obscure.