Advanced hepatocelluar carcinoma (HCC) has a poor prognosis. In this study, the authors evaluated the efficacy of chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), and leucovorin (LV), comparing our regimen with chemotherapy using CDDP and 5-FU. Nineteen patients with advanced HCC were treated by arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port. In Group A (n=9), one course of chemotherapy consisted of the daily administration of CDDP (10 mg/1 h, on 5 days) and LV (12 mg/10 min, on 5 days) followed by 5-FU (250 mg/5 h, on 5 days). In Group B (n=10), except for the administration of LV, the same regimen was employed. This course was repeated each week for 4 weeks. In Group A, two patients showed a complete response (CR), and the other three showed a partial response (PR). In Group B, two patients showed PR. The response rate (CR+PR/all cases) in Group A was significantly higher than that in Group B (56 vs. 20%; P=0.022). The 1- and 2-year survival rates of Group A (66.7, 44.4%) were significantly higher than those of Group B (10, 0%) (P=0.033). These results suggest that our regimen may be useful in treating patients with advanced HCC.