We retrospectively examined patients with advanced gastric cancer who underwent gastrectomy following neoadjuvant chemotherapy (NAC) with S-1 plus weekly low-dose cisplatin (CDDP). Between 2007 and 2009, 27 patients with advanced gastric cancer not amenable to curative surgery were enrolled. One course of NAC comprised S-1 (80 mg/m2/day) for 21 consecutive days and CDDP (20 mg/m2) on days 1, 8, and 15; this was followed by a 2-week rest after the end of S-1 administration. Grade 3 side effects were observed in 5 patients: 3 experienced neutropenia and 2 experienced digestive symptoms. The outpatient completion rate was 81.5% (22/27); there was no incidence of renal dysfunction. During pretherapy diagnosis, depth of invasion was classified as T4 in all cases. Postoperative pathologic results showed that the depth of invasion was T3 or lower in 4 patients. In addition, the number of patients with N0 and M0 classification increased and downstaging was observed in 12 patients (44.4%). A comprehensive assessment revealed that a partial response (PR) was observed in 13 patients and stable disease (SD) was observed in 12 patients, resulting in a response rate of 48.1%. The median survival time was 580 days, and the 1-year survival rate was 72%. NAC with S-1 plus weekly low-dose CDDP can also be administered on an outpatient basis, and it is a potential regimen for the treatment of advanced gastric cancer associated with a poor prognosis.