Conclusion: It appears that patients with SCCHN should be recommended to take S-1 for more than 1 year and, if possible, more than 2 years, as adjuvant chemotherapy for SCCHN. Objectives: There is no established consensus on the duration of administration of S-1 as adjuvant chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). Since it might be difficult to undergo prospective randomized study to identify the optimal duration of the administration period of S-1 without a standard, the authors have undergone a retrospective clinical study to decide the tentative standard of therapeutic duration of S-1 as adjuvant chemotherapy for SCCHN. Methods: The clinical records of 89 patients with SCCHN who underwent adjuvant chemotherapy with S-1 were investigated. Results: The median duration of S-1 administration as adjuvant chemotherapy for SCCHN was 7 months (range = 0.1-58 months). Disease-free survivals (DFSs) were generally longer when S-1 administration periods were longer. After adjusting for prognostic factors, S-1 administration periods of 24 months or longer showed significantly lower hazard ratios (HRs) than 0-12 months.