The X-linked inhibitor of apoptosis (XIAP) belongs to the inhibitor of apoptosis (IAP) family, and the action of XIAP is inhibited by XIAP-associated factor-1 (XAF1). In the present study, XIAP and XAF1 protein expressions and their relationship to apoptosis were investigated in hepatocellular carcinoma (HCC). We examined immunohistochemical expressions of XIAP and XAF1, and the number of apoptotic HCC cells in surgically resected tissues of 24 HCCs, consisting of 7 well-, 10 moderately and 7 poorly differentiated HCCs. As a result, XIAP and XAF1 expressions were identified in the cytoplasm of non-neoplastic and neoplastic hepatocytes. In the 24 HCCs, XIAP expression was not different according to the histological grade of HCC. In contrast, XAF1 expression was significantly lower in poorly differentiated than that in well- or moderately differentiated HCCs (P=0.001), or XIAP expression in poorly differentiated HCC (P<0.001). Apoptotic HCC cell number was significantly lower in poorly differentiated than that in well- or moderately differentiated HCCs (P<0.01). A significant relationship was observed between XAF1 expression and apoptotic cell number in HCC tissues. In conclusion, the present findings suggest that significantly low XAF1 expression, but not XIAP expression, in poorly differentiated HCC may relate to resistance to apoptosis.