Several chemotherapy regimens used against advanced gastric cancer have been studied extensively over the decades in an attempt to further improve the prognosis of patients. To date, no standard chemotherapeutic regimens have been established worldwide. S-1 (TS-1), a combination of ftorafur and two modulators, gimestat (CDHP) and oxonic acid, in a molar ratio of 1:0.4:1, has been widely used in Japan for the treatment of advanced gastric cancer, and much attention has been paid to attempts to increase its antitumor effect by combining it with other chemotherapeutic drugs. We treated 12 patients with advanced gastric cancer with 80 mg/m2 of S-1 for 21 days and 60 mg/m2 of cisplatin (CDDP) on day 8 every 5 weeks. The treatment was continued until disease progression, unacceptable toxicity, or the patient's refusal. Eight out of 12 evaluable patients achieved a partial response (PR), with a response rate of 66.7%. The incidence of grade 3 or 4 adverse effects, including myelosuppression and gastrointestinal toxicities, was 16.6%. None of the patients treated with this regimen died of adverse effects and none required hospitalization for the toxicity. We conclude that the combination of S-1 and CDDP seems to have a high therapeutic index, enhancing the antitumor effect of S-1 while maintaining modest adverse effects, thus suggesting the possible use of this combination based at the outpatient clinic (apart from a short stay in hospital during the infusion of CDDP with hydration). Further study with a large number of patients may be needed to confirm the combination of S-1 and CDDP to be an appropriate first-line chemotherapy for gastric cancer.