A 54-year-old man maintained on hemodialysis had a relapse of multiple pulmonary metastases after multimodal therapy for primary hepatocellular carcinoma (HCC). He was treated with tegafur-uracil (UFT; 400 mg/day) and interferon alfa (IFN-alpha; 5 x 10(6) units three times per week) for 4 weeks. Following this he was treated with systemic 5-fluorouracil (5-FU; 1000 mg/day, 5 days per week) and cisplatin (CDDP; 10 mg/day, 5 days per week for 2 weeks). The response to the above treatments was inadequate; pulmonary metastasis deteriorated. Finally, we selected systemic chemotherapy of 5-FU (750 mg/day, 5 days per week) and recombinant IFN-alpha-2b (3 x 10(6) units three times per week) for 2 weeks. This therapy resulted in excellent shrinkage of pulmonary metastases, without severe adverse reactions. Hemodialysis was performed three times a week. We report a case of successful treatment of pulmonary metastases by systemic combination chemotherapy of 5-FU-IFN, previously unsuccessfully treated with UFT-IFN and 5-FU-CDDP in a patient on hemodialysis. Further studies are needed to select appropriate drugs with fluoropyrimidine-based systemic chemotherapy, and to analyze the pharmacokinetics of those agents in hemodialysis patients with HCC and extrahepatic metastases.