Objective To select a best mouse strain for establishing an animal model of orthotopic transplanted liver cancer through comparison analysis.Methods C57,C3H and BALB/c mice(each 10)were selected as model groupⅠ,Ⅱ and Ⅲ.H22 cells were inoculated into the liver parenchyma of mice in model group along the ventral midline laparotomy.Fifteenth days after injection of laparotomy,the rate of tumor was observed,the volume of ascites and gross tumor volume were measured,and tumor pathology was analyzed.Results The survival rate of mice in three groups was 100%.After 15 days,ascites in three groups were produced,but with no significant difference among the three groups of the volume of ascites.Tumor transplantation rate in model groupⅠ was 100%,which was higher than 60% in model group Ⅱ and 30% in model group Ⅲ.Liver tumors in model group Ⅰ were all large compact grayish white lesions,and the average tumor volume was significantly greater than that of model group Ⅱ and Ⅲ(P< 0.05). Pathology results confirmed that white lesions in liver of three groups were hepatocelluar carcinoma in situ.Conclusion C57 is the better ideal experimental animal for establishing orthotopic liver caner model,and these results will provide a good experimental platform for research in pathogenesis of hepatocellular carcinoma.