S-1 chemotherapy is widely used to treat head and neck cancer. Reports of interstitial pneumonia as a side effect of S-1 chemotherapy are very rare.<br>We report a case of interstitial pneumonia possibly caused by S-1 treatment as postoperative adjuvant chemotherapy.<br>We gave S-1 as postoperative adjuvant chemotherapy for mandibular gingival carcinoma in a 80-year-old woman. She had a fever 53 days after starting S-1 chemotherapy. The X-ray films and computed tomography （CT） showed reticular shadows in both lung fields, and the patient was given a diagnosis of interstitial pneumonia. The results of a drug-induced lymphocyte stimulation test were positive against S-1. The total dose of S-1 until the onset of symptoms was 3360 mg. We immediately started steroid therapy and withdrew S-1 chemotherapy, and then the symptoms remarkably improved, as did the abnormal findings on CT.<br>In conclusion, when a patient has a high fever and dyspnea during S-1 therapy, drug-induced interstitial pneumonia should be included in the differential diagnosis.