[Objective] To observe the pathological changes in the livers of p21 HBsAg/HBsAg transgenic mice. [Methods] The p21 HBsAg/HBsAg transgenic mice(2,6,12, 18, 24 months) in SPF grade and corresponding p21 +/+ mice were dissected and the liver and hepatic tumor tissues were extirpated for the examination by histological HE staining and electron microscopy. [Results] Distinct pathological changes appeared in the liver of p21 HBsAg/HBsAg transgenic mice both macroscopically and microscopically. With the increase on age, the liver of the transgenic mice turned to be dark and sclerotic with scattered formation of nodules and tumors. Under light microscope, the liver cells were swollen and inflammatory cell infiltration occurred. Fatty degeneration appeared with punctuate, focal and crumblike necrosis. Atypical hyperplasia and hepatocellular carcinoma (HCC) developed. Resembling normal hepatocytes, hepatpocarcinoma cells were well differentiated, forming cord-like and acinar-like structures. The nuclei of carcinoma cells are dark stained with karyokinetic figures and aberrated with invagination of nuclear membrane under electron microscope. Mitochondria distended, manifolded and the ridges reduced. HCC were found in four cases of 18 months old p21 HBsAg/HBsAg transgenic mice (4/10, 40%), and six cases of 24 months (6/10,60% ) respectively, of which metastasis occurred in two cases. [Conclusions] Obviously pathogenic changes occurred in the liver of p21 HBsAg/HBsAg transgenic mice. Well differentiated hepatocarcinoma became to arise in the mice at the age of 18 months. Metastasis of HCCs would happen in elderly transgenic mice.