BACKGROUND: Nerve growth factor (NGF) has been suggested to participate in tumor progression and it can interact with its receptor p75NGFR. In the present study, we investigated the expressions of NGF and p75NGFR in hepatocellular carcinoma (HCC). METHODS: We performed immunohistochemistry for NGF, p75NGFR and PCNA in 45 cases of HCCs, and examined the relationships between the clinicopathologic factors and the immunohistochemical results. RESULTS: NGF was detected in 84.4% (38/45) of the tumor cells and in 64.4% (29/45) of the non-tumorous hepatocytes. Furthermore, a NGF expression was present in 28.9% (13/45) of the endothelial cells in the HCCs, but in 80% (36/45) of the endothelial cells in the non-tumor liver tissue. The tumor cells were negative for p75NGFR in all the HCCs. Although a p75NGFR expression was present in all the nerve fibers in the non-tumor liver tissues, it was markedly reduced (42.2%; 19/45) in the HCCs and a p75NGFR expression was observed at the sinusoids or around the large vessels. The HCCs expressing NGF, either in the tumor cells or the endothelial cells, showed a larger size than those HCCs that didn't express NGF. The NGF positive tumors showed a tendency toward a higher PCNA-labeling index than did the negative tumors. CONCLUSIONS: The changed localization of the NGF expression and the decreased expression of p75NGFR are associated with hepatic carcinogenesis. We suggest that a NGF expression may contribute to the progression of HCC.