We experienced a 49-year-old man with cancer of the lower lip (squamous cell carcinoma, T1N2cM0). We planned surgical treatment including bilateral neck dissection and started a new TS-1 administration method as a neo-adjuvant chemotherapy. One course of this chemotherapy consisted of 3 weeks'administration including 5-day administration and 2-day termination following 1 week rest. TS-1 was given at 120 mg/day. After the first course of chemotherapy, the primary tumor disappeared, and the neck lymph node metastases were markedly reduced. There was no obvious side effect except mild stomatitis. Since we assumed that the lymph node palpated in left neck was a residual tumor, we performed left neck dissection. Histopathological examination revealed that there was no cancer cell but hyalinization in the removed specimen of lymph node, suggesting that the effect of the chemotherapy was a pathologically complete response. We concluded that our novel TS-1 administration method was extremely effective for head and neck squamous cell carcinomas with high potential and without any severe side effects.