AIM: To study the distribution pattern of transcription factors NF-κB and AP-1 and their relations with the expression of apoptosis associated-proteins Fas/FasL and ICH-1L/S in human hepatocellular carcinoma (HCC).METHODS: We performed in situ hybridization and immunohistochemical techniques for NF-κB, AP-1,Fas/FasL and ICH-1 in 40 cases of human HCC along with corresponding nontumoral tissues and 7 cases of normal liver tissues.RESULTS: Twenty-two (55%) and 25 (62.5%) of 40 cases for NF-κB and AP-1 were presented for nuclear or both nuclear and cytoplastic staining respectively, while less cases were presented for only cytoplastic staining for NF-κB (18%) and AP-1 (10%) in adjacent nontumoral tissues and negative staining in normal liver tissues. There was no statistically significant difference of NF-κB or AP-1activation between well differentiated tumors and poorly differentiated tumors (P＞0.05). NF-κB activity is positively corresponded to AP-1 activation. The expression of ICH-1L/S was associated with the activation of NF-κB and AP-1 (P＜0.05), but no significant relationship was found between Fas/FasL and NF-κB or AP-1(P＞0.05).CONCLUSION: Activation of both NF-κB and AP-1 may be required for ICH-1L/S-induced apoptosis in HCC, but not for Fas/FasL-mediated apoptosis. NF-κB and AP-1may play important roles in the pathogenesis of human HCC.