We determined the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and efficacy of drug sequence on toxicities of the combination of S-1 and docetaxel for head and neck cancers. S-1 was administered at the full dose of 80 mg/m2 for two weeks and docetaxel on day 1 according to the following dose escalation schedule: level 1: 40 mg/m2, level 2: 50 mg/m2, and level 3: 60 mg/m2. DLT was observed in two cases of level 3. Although grade 3 leukopenia was observed in level 3, all of the toxicities were not severe. Recommended doses for the next phase evaluation were determined to be 80 mg/m2 of S-1 and 50 mg/m2 of docetaxel. Oral S-1 combination with docetaxel is a feasible and promising combination regimen that is appropriate for an outpatient setting.