AIM: To investigate the expression of metallothioneins (MTs), which were recently thought to have close relationship with tumors, in human hepatocellular carcinoma. METHODS: Histological specimens of 35 cases of primary human hepatocellular carcinoma with para-neoplastic liver tissue and 5 cases of normal liver were stained for MTs with monoclonal mouse anti-MTs serum (E9) by the immunohistochemical ABC technique. RESULTS: MTs were stained in the 35 cases of HCC, including 6 cases negative (17.1%), 23 weakly positive (65.7%), and 6 strongly positive(17.1%). But MTs were stained strongly positive in all the five cases of normal liver and 35 cases of para-neoplastic liver tissue. The differences of MTs expression between HCC and normal liver tissue or para-neoplastic liver tissue were highly significant (P<0.01). The rate of MTs expression in HCC grade I was 100 percent, higher than that in grade II(81%) and grade III and IV (78%). But the differences were not significant (P>0.05). No obvious correlations between MTs expression in HCC and tumor size, clinical stage or serum alpha fetoprotein concentration were found (P>0.05). CONCLUSION: Decrease of MTs expression in HCC may play a role in carcinogenesis of HCC. MTs are stained heterogenously in HCC. We can choose the anticancer agents according to the MTs concentration in HCC, which may improve the results of chemotherapy for HCC.