Abstract: Objective To explore the differential expression of CK19 in the process of chemical carcinogenesis of liver cancer for C57BL/6J mice. Methods The experimental group was 50 male C57BL/6J mice which were induced primary liver cancer by chemical,and 50 normal male C57BL/6J mice were as the control group which was raised normally.The mice were killed every 4 weeks to collect the specimen and detect the changes of CK19 gene and protein by RT-PCR,FQ-RT-PCR and Western blot methods,at the same time,pathological changes were observed through HE Stain. Results The results showed that the experimental mice had obvious nodules after 16 weeks chemical incuction,the size of the nodules was between 2mm and 25mm in diameter.The pathological changes showed well-differentiated hepatocellular carcinoma with the features of structure disorder,dysplasia,pathological mitotic and part of liver tissue cirrhosis.RT-PCR,FQ-RT-PCR and Western Blot showed that CK19 was not highly expressed in the liver tissue of the experimental group mice till after 16th weeks.The mRNA level of CK19 in HCC tissues of 4th,8th,12th,16th and 20th week were separately(2.133±0.470),(2.395±0.472),(2.767±0.729),(3.217±0.627),and (14.095±5.812),it was markedly higher than that of the corresponding control group at the same stage (P<0.05). Conclusion The liver cancer stem cell marker CK19 gene maybe involve in the occurrence and development of HCC,but the regulatory mechanism of CK19 in the process of chemical carcinogenesis is not quite clear and worth of further exploration.