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OBJECTIVE To determinate the effect of thoracic duct ligation during thoracoscopic esophagectomy on esophageal cancer patients survival. STUDY DESIGN A descriptive study. PLACE AND DURATION OF STUDY Tai'an City Central Hospital, Tai'an, Shandong, China, from June, 2016 to June, 2021. METHODOLOGY All cT1b-3N0M0 stage esophageal cancer patients were randomly divided into thoracic duct ligation group and non-ligation group. In addition to thoracoscopic esophagectomy, thoracic duct ligation was also performed in the experimental group. The general data of two groups were compared by Chi-square test, with statistical significance at p <0.05. The effect of thoracic duct ligation on disease-free survival (DFS) and overall survival (OS) was analysed by Kaplan-Meier and Cox regression. RESULT There was no significant difference in gender, age, tumor location, depth of invasion, degree of differentiation and presence of tumor thrombus between the ligation group (33 cases, 47.8%), and the non-ligation group (36 cases, 52.2%). Cox regression analysis showed that depth of invasion (p = 0.0014), degree of differentiation (p = 0.0036), presence of tumor thrombus (p = 0.0367) and thoracic duct ligation (p = 0.0057) were independent factors affecting DFS. Meanwhile, the depth of invasion (p <0.0001), presence of tumor thrombus (p = 0.0073) and age (p = 0.0129) were independent factors affecting OS. CONCLUSION Thoracic duct ligation during thoracoscopic esophagectomy can affect DFS in patients with pT1b-3N0M0 esophageal squamous cell carcinoma, and the thoracic duct ligation, depth of invasion, degree of differentiation and presence of tumor thrombus are independent factors. Meanwhile, the depth of invasion, presence of tumor thrombus and age were independent factors affecting OS. Key Words: Esophageal cancer, VATS, Esophagectomy, Thoracic duct ligation, DFS, OS.