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Background/Aims: This study documents the clinical efficacy and toxicity of S-1 and paclitaxel (S1/PTX) in patients with unresectable or postoperative recurrent esophageal squamous cell carcinoma (ESCC) who had been previously treated with fluorouracil (5FU), cisplatin, and docetaxel. Methods: Twenty-eight ESCC patients treated using S1/PTX at our institute since 2010 were enrolled in this study. S1 was administered orally at a dose of 80 mg/m2/day from days 1 to 14, and PTX was administered intravenously on days 1 and 8 at a dose of 80-100 mg/m2. Results: A total of 106 cycles (median 2.5 cycles, range 1-12 cycles) were administered. The response rate was 14.8%, including 3 complete responses. The median progression-free survival time was 137 days, and the median overall survival time was 306 days. Severe neutropenia occurred in 13 patients, and 3 showed febrile neutropenia. All non-hematological toxicities were mild, and peripheral nerve paralysis was observed in 2 patients. Conclusion: S1/PTX was found to have tolerable clinical efficacy in terms of the response rate, survival and toxicity in patients with unresectable or postoperative recurrent ESCC who had previously been treated with 5FU, cisplatin, and docetaxel. [ABSTRACT FROM AUTHOR]