Despite the improvement in the operative results for patients with gastric cancer, the prognosis of those with liver metastasis remains dismal. Multimodal therapy has attracted considerable attention as a breakthrough in the strategy for treating cases of highly advanced gastric cancer. We report the case of a 62-year-old female with gastric cancer accompanied by multiple liver metastases successfully treated by TS-1, a novel oral fluoropyrimidine derivative. One treatment course consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. After 3 courses of treatment, an abdominal CT scan showed no evidence of liver metastases and gastroscopy revealed that the primary gastric lesion was reduced. Grade 1 toxicity (nausea and diarrhea) was seen but 6 days rest improved the condition. Distal gastrectomy was subsequently performed without any finding of residual tumor. TS-1 may have a promising role in neoadjuvant chemotherapy for gastric cancer.