Hepatitis C virus (HCV) core protein is considered an important viral structural protein and has been known to regulate proliferation and apoptosis of the cells, thus, it is belived to be related to cirrhosis of liver and hepatocarcinogenesis resulting from HCV infection. To further study the relationship between HCV core protein and hepatocarcinogenesis. The eukaryote expressing recombinant plasmid vector were constructed, then transferred it into human hepatocyte-derived Chang-liver cell line by lipofectin and established the cell model expressing HCV core protein. HCV core mRNA in the Chang-liver cells was detected by RT-PCR. Expression and distribution of the HCV core protein in the Chang-liver cells were identified by Western blot and immunocytochemistry (ICC). Phenotype of the cells expressing HCV core protein altered and displayed long fusiform shape under light microscope cultured more than 20 passages after transfection, Compared with control group cells, the cells showed a markedly increased proliferation rate, and a higher variation index of DNA content. 6/6 of BALB/c-nu/nu nude mice generated tumors until 20 days after subcutaneous inoculation of the cells expressing HCV core protein. Furthermore, constitution structure of the tumors coincided with that of hepatocarcinoma. Control group nude mice did not generated tumors. Above results indicated that HCV core protein promoted the malignant transformation of the Chang-liver cells, which implied that HCV core protein was directly related to hepatocarcinogesis result from HCV infection.