We encountered a case of gastric cancer accompanied with liver metastasis, which had a good response to chemotherapy of S-1. A 68-year-old female was admitted to our hospital due to further examination of gastric tumor detected by an outpatient physician. She was found to have a type-3 gastric cancer in upper gastrointestinal endoscopy and a metastatic tumor of the liver in abdominal CT. Although chemotherapy of S-1 was inducted for the lesions, both the primary and liver tumors were dramatically reduced. We subsequently performed total gastrectomy and partial hepatectomy. Abdominal CT scan at 11 months after the initial operation revealed metachronous liver metastasis. She received combination chemotherapy of S-1 and CDDP. After 5 courses of the combination chemotherapy, the liver tumor disappeared. She has survived for 8 years without a recurrence after the initial operation. There was negative findings of immunostaining with thymidylate synthetase (TS), which was target enzyme for 5-FU at a biopsy sample of the primary gastric tumor before chemotherapy of S-1. TS immunostaining may be a useful marker for S-1 combined therapy for gastric cancer associated with liver metastases.