We report a case of advanced gastric cancer that responded completely to S-1 neoadjuvant chemotherapy. An 80-year-old female complained of nausea. A gastroscopy and CT scan revealed advanced gastric cancer with lymph node metastasis (cT4b [diaphragm], cN3a, cM0, cStage III C). S-1 (100 mg/body/day) was administered orally for 14 consecutive days followed by a 7-day interval. After 2 courses of monotherapy, we conducted a total gastrectomy with D2 lymph node dissection. Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes. This meant that the resected lesions were pathologic Grade 3. Our report suggests that S-1 may have a potent therapeutic effect as a neoadjuvant chemotherapy for advanced gastric cancer especially in older patients.