We used a new combination chemotherapy with nedaplatin (CDGP) and 5-fluorouracil (5-FU) in eleven fresh patients with oral squamous cell carcinomas. 5-FU was administered at a dose of 1,000 mg/body by continuous infusion for 24 hours on days 1 to 5. CDGP was administered at a dose of 80 or 100 mg/m2 by drip infusion for 120 minutes on day 5. The response rates of total (1- or 2-course) and 2-course group were 54. 5% and 83.3%, respectively. Adverse drug reactions were limited to two cases of grade 3 toxicity with anorexia. The combination chemotherapy with 5-FU and CDGP in place of cisplatin and 5-FU seemed to play an important role as neo-adjuvant chemotherapy for oral squamous cell carcinomas.