Objective: The role of chemotherapy in locally advanced head and neck cancer has been established in nasopharynx and larynx as definitive therapy and organ preserving therapy, respectively. Oral cavity cancers are relatively uncommon and local recurrence is the main cause of treatment failure. We planned this retrospective study to evaluate the role of neoadjuvant chemotherapy in locally advanced oral cavity cancer patients. Materials and Methods: From 1988 March to 2001 February, locally advanced, previously untreated oral cavity cancer patients who received neoadjuvant chemotherapy were examined. Chemotherapy had been done in the following patients: Histologically proven squamous cell or poorly differentiated carcinoma, stage 3 or 4, and performance state 0-2 patients. Chemotherapy regimen consisted of cisplatin and infusional 5-fluorouracil. Response was evaluated after 2 cycles and in case of no response, definitive local therapy was done; otherwise 3 cycles was done before local treatment. Results: 48 patients were treated and 47 patients were evaluable for responses. Complete response rate was 6.4%(3/47) and partial response 80.0%(38/47), scoring overall response rate of 87.2%. Median time to progression was 27.0 months (95% CI : 0-58months) and overall 5 year survival was 54.8%. 5-year disease-free survival in the patients in remission after local treatment was 51.9%. In multivariate analysis, contributing factor to the survival were response to neoadjuvant chemotherapy and local treatment modalities. Extensive surgery was done in 10 patients and 25 patents (52.1%) was followed up with preserved function. With median follow-up of 57.0 months, 19 recurrences were detected, most of which were local or regional type. Conclusion: Neoadjuvant chemotherapy followed by local treatment in oral cavity cancer showed high response rate and was thought to be effective therapeutic approach especially in view of organ preservation.