S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used as a chemotherapeutic agent in the treatment of various carcinomas. This study was performed to assess the efficacy and safety profile of the combination of S-1 and cisplatin(S-1/CDDP)in patients with oral cancer as neo-adjuvant chemotherapy. We reviewed our experience of 12 patients diagnosed with oral carcinoma, who were treated with S-1/CDDP. S-1 was administered orally at a dose of 50mg twice a day for 21 consecutive days, followed by a 14-day rest period. CDDP(60mg/m2)in 500 mL physiological saline was administered by intravenous drip as a 120-min infusion on day 8, together with standard premedications and hydration. Seven partial responders were obtained. The median follow-up duration was 54. 8 months, and all patients were alive excluding one case. This regimen was well tolerated, with only one case of grade 3 thrombocytopenia, and no grade 4 patient. No treatment-related death was observed. Moreover, we evaluated immunohistochemical expressions of thymidylate synthase (TS), dihydropyrimidine dehydrogenase(DPD), and orotate phosphoribosyl transferase(OPRT)which are associated with chemosensitivity to 5-FU-based therapies. We investigated the relation between the immunohistochemical score and clinicopathological factors, however we could not clarify the relationship between the efficacy of chemotherapy and results of immunohistochemistry.