We found that miR‐2355‐5p inhibitor dramatically suppressed the levels of p‐JAK2 and p‐Stat5 proteins, but miR‐2355‐5p mimic extremely promoted the expressions of p‐JAK2 and p‐Stat5 in ESCC cells; however, the effects were reversed by WDFY3‐AS2 down‐regulation or overexpression. This evidence concerns the gene WDFY3 and esophageal squamous cell carcinoma.