We describe our experience with a patient who had advanced hepatocellular carcinoma (HCC) that responded markedly to treatment with the oral fluoropyrimidine anticancer drug S-1 (120mg/day/body bid on day 1 through 28 followed by a 14-day recovery period). The patient was enrolled in a phase I / II study designed to evaluate the safety and efficacy of S-1 in patients with advanced HCC. The best overall efficacy was confirmed to be a partial response (PR). After a total of 6 courses of treatment given on an outpatient basis, the target lesion volume decreased by 73. 8%. With regard to adverse events, the patient did not develop Grade 3 or higher adverse drug reactions. Therefore, the patient continued outpatient treatment for a total of 6 courses. The duration of survival from the start of treatment until death was 820 days, suggesting that S-1 is moderately effective and well tolerated in patients with advanced HCC.