Objective:To investigate the effects and mechanisms of vortioxetine on the proliferation and migration of esophageal squamous cell cancer.Methods:CCK-8 assay was used to detect the viability of Eca109 and KYSE150 cells after treated with vortioxe-tine at different concentrations(0,2,4,6,8,10 μmol/L).Moreover,transwell and scratch assays were employed to evaluate the migra-tion of ESCC cells,plate colony formation assay was used to detect the proliferation.The differentially expressed genes were screened by TCGA database,AutoDock software was used to predict the binding of vortioxetine and cyclooxygenase-2(COX-2)protein.Further-more,the expression of COX-2 mRNA and protein were measured by RT-qPCR and Western blot,respectively.Results:The cell viabil-ity of Eca109 and KYSE150 decreased in a concentration-dependent manner after treatment with different concentrations of vortioxetine(P<0.05),and the semi-inhibitory concentrations(IC50)were 5.086 μmol/L and 5.179 μmol/L,respectively.Compared with the control group,the cell proliferation and migration of the vortioxetine group were reduced(P<0.05).In addition,vortioxetine could in-hibit the expression of COX-2 at mRNA and protein level(P<0.05).Conclusion:Vortioxetine inhibits the proliferation and migration of esophageal cancer cells probablly through COX-2 down-regulation.