Background: To assess the efficacy of neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (CRT). Methods: The clinical data of patients with ESCC treated with chemoradiotherapy with or without NAC were collected and retrospectively reviewed. The overall survival, locoregional failure-free survival, and distant failure-free survival were analyzed statistically. Results: A total of 60 patients fulfilled the inclusion criteria, of which 41 were treated with NAC-CRT and 19 were treated with CRT-alone. Patient characteristics were well balanced between the NAC-CRT and CRT-alone groups, except for the ECOG scores. The tumor response to NAC included 11 patients (26.8%) with partial response (PR), 25 patients (61.0%) with stable disease (SD), 5 patients (12.2%) with progression disease (PD), and no patients with complete response (CR). After CRT, 21 patients achieved CR (14 after NAC-CRT and 7 after CRT alone), 30 had PR (19 and 11,.respectively), 6 maintained SD (5 and 1, respectively), and 3 patients (all in the NAC-CRT group) developed PD. Twenty-nine patients (18 in NAC-CRT and 11 in CRT-alone) succumbed to the disease from locoregional or distant failure, one patient in the NAC-CRT group died of radiation pneumonitis, one patient in the CRT-alone group died from unknown reasons, and 29 patients remained alive. The overall survival, locoregional failure-free survival, and distant failure-free survival at 1 and 2 years in all the patients were 64.9% and 40.5%, 58.6% and 52.0%, and 85.7% and 79.3%, respectively. The overall survival, locoregional failure-free survival, and distant failure-free survival between the NAC-CRT group and the CRT-alone group were not significantly different. Conclusion: In patients with ESCC treated with definitive CRT, NAC treatment using the current regimen does not prolong overall survival, locoregional failure-free survival or distant failure-free survival. Further development of NAC treatment is urgently needed. Copyright (C) 2017, the Chinese Medical Association. Published by Elsevier Taiwan. LLC.