We experienced a case of advanced gallbladder cancer with a remarkable response treated by oral fluoropyrimidine anticancer drug S-1 (120 mg/day on day 1 through 28 followed by a 14-day recovery period) as first-line chemotherapy. The patient was enrolled in the late phase II trial of S-1 for metastatic biliary tract cancer designed to evaluate efficacy and safety. The anti-tumor effect was observed in both primary lesion of gallbladder and metastatic lesion of liver,and the efficacy was confirmed to be a partial response (Japan Society for Cancer Therapy Criteria). After the first two courses of treatment, the reduction ratio of the tumor volume was 88.1% in the measurable lesions of liver metastasis. No severe adverse event was noted except grade 3 desquamation. The patient continued the outpatient treatment for a total 7 courses. The overall survival time was 470 days,suggesting that S-1 is highly effective and tolerable for metastatic gallbladder cancer.