Long-term postoperative survival and prognostic factors were examined retrospectively in patients with hepatocellular carcinoma (HCC) with serum hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb) and in those without virus infection. Subjects were 265 consecutive HCC patients treated surgically at one institution during the period 1990 to 2006. Postoperative survival was analyzed and compared between HBsAg-positive (B-HCC), HCVAb-positive (C-HCC), and hepatitis B- and C-negative (NBNC-HCC) patients. Prognostic factors for overall and recurrence-free survival were also analyzed. Overall and recurrence-free survival rates were significantly higher in the NBNC-HCC group than in the C-HCC group. Significant prognostic factors for overall survival identified by univariate and multivariate analyses were age, serum alkaline phosphatase (ALP) level, tumor multiplicity, portal vein invasion (Vp), hepatic vein invasion (Vv), and operative blood loss in the B-HCC group; serum albumin level, ALP level, tumor size, and Vv in the C-HCC group; and tumor multiplicity in the NBNC-HCC group. Significant factors for recurrence-free survival were age, ALP level, tumor multiplicity, Vp, and operation time in the B-HCC group; ALP level, prothrombin time, tumor size, Vv, and width of the surgical margin in the C-HCC group; and age, tumor size, tumor multiplicity, and Vp in the NBNC-HCC group. Thus, postoperative survival and prognostic factors in cases of HCC differ according to the presence of serologic viral markers.