Most importantly, ZEB1‐AS1 down‐regulation markedly suppressed ZEB1 expression, whereas ZEB1 overexpression reversed the biological effect mediated by ZEB1‐AS1 down‐regulation in vitro and in vivo, which was tightly associated with the changes in EMT markers including E‐cadherin, N‐cadherin and vimentin, suggesting ZEB1‐AS1 functions as oncogene by regulating ZEB1 expression in ESCC cells. This evidence concerns the gene CDH2 and esophageal squamous cell carcinoma.