Objective:To investigate the influencing factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC), and to compare the clinical prognosis of ESCC patients with and without pCR after NCRT (40 Gy/ 20F).Methods:Among patients enrolled in a prospective clinical study, 87 ESCC patients treated with NCRT followed by surgery in Tianjin Medical University Cancer Institute & Hospital between June 2015 and October 2019 were selected. They were divided into the pCR ( n=35) and non-pCR groups ( n=52). Clinicopathological characteristics were retrospectively analyzed and subsequent follow-up was performed. Clinical prognosis and influencing factors were compared between two groups by using Kaplan-Meier and Cox regression analyses. Results:After NCRT, 40% of the ESCC patients could achieve pCR. Univariate analysis showed that patients in the pCR group had a disease-free survival (DFS) of 39.3 months and an overall survival (OS) of 64.0 months. In comparison, patients in the non-pCR group had a DFS of only 14.1 months and an OS of only 25.2 months. The differences were statistically significant (DFS: P<0.01, OS: P<0.05). Multivariate analysis revealed that whether pCR or not after NCRT, age, number of primary lesions, evaluation results after NCRT and postoperative pathological outcomes were important prognostic factors. The differences were statistically significant between two groups (all P<0.05). Conclusion:pCR after NCRT is significantly correlated with long-time survival of patients with ESCC, and pCR after NCRT has an important value in predicting clinical prognosis for long-term survival of ESCC patients.