We report a case of advanced hypopharyngeal carcinoma that responded well to chemotherapy with TS-1, a novel oral anticancer agent of fluorinated pyrimidines. The patient was a 65-year-old man who underwent radiation therapy at 64.8Gy as first-line therapy. The treatment resulted partial response of the primary tumor, while the metastatic cervical lymph node did not show any change. After discharge, the patient received intermittent 80mg/day of oral TS-1 for 2 weeks of every 3 weeks. CT after 5 months demonstrated disappearance of the primary tumor and partial response in the metastatic lymph node. TS-1 administration still continus, and the patient has shown a good course. We considered that TS-1 is effective against the noncurable head and neck squamous cell carcinoma and allows the patient to maintenance satisfactory QOL.