Background: Docetaxel and cisplatin, 5-FU (DCF) therapy has established as the standard neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 study. If patients showed recurrence of ESCC after neoadjuvant DCF therapy, platinum-containing regimens were used as palliative treatment in the clinical practice. However, there were no data of correlation between histopathological response by neoadjuvant DCF therapy and clinical efficacy of palliative platinum-containing regimens for recurrent ESCC. Methods: We retrospectively reviewed patients with ESCC who received neoadjuvant DCF therapy and R0 resection between Feb 2014 to June 2022 in our hospital. We evaluated histopathological response by neoadjuvant DCF therapy based on the Japanese Classification of Esophageal Cancer 12^th (Grade 0: ineffective, Grade 1: slightly effective, Grade 2: moderately effective, Grade 3: markedly effective [pT0]) and objective response rate (ORR), progression-free survival (PFS) during platinum-containing regimens as clinical efficacy outcomes. We analyzed the correlation between histopathological response and ORR, PFS using Fisher’s exact tests and the log-rank tests. In addition, we analyzed clinical factors related to clinical efficacy of palliative chemotherapy using Cox proportional hazards models. Results: In this study, 398 patients received neoadjuvant DCF therapy and we identified 88 eligible patients with recurrence. Among 88 patients, 33 patients initially received palliative chemotherapy and analyzed. Patients’ characteristics were followed; Male/Female: 26 (78.8%)/7 (21.2%), median age (range): 64 (46-76) years, PS 0/1/2: 1 2(36.4%)/17 (51.5%), 4 (12.1%). Histopathological response 0/1/2/3 were in 1 (3.0%)/23 (69.7%)/7 (21.2%)/2 (6.1%) patients, respectively. Among these 33 patients, 23 patients received platinum-containing regimens. In the patients who received palliative chemotherapy, the ORR were 34.8% (8/23) in histopathological response 0/1 group and 44.4% (4/9) in histopathological response 2/3 group, with no statistical difference (p = 0.696). The median PFS was 2.43 (95%CI: 2.33-2.53) months in histopathological response 0/1 group and 4.04 (95%CI: 0-10.77) months in histopathological 2/3 group (HR[95%CI]: 1.121 [0.413-3.043]). Multivariate analysis using Cox proportional hazards models revealed chemotherapy-free-interval (CFI) < 6 months (HR[95%CI]: 3.594 [1.027–12.580]) was independent prognostic factor, whereas histopathological response didn’t show the significance (HR[95%CI]: 0.723 [0.195–2.678]). Conclusions: Histopathological response by neoadjuvant DCF therapy did not affect the efficacy of platinum-containing regimens for recurrent ESCC, while CFI might be the prognostic factors.