We demonstrated that miR‐99a‐5p could inhibit TRIB2 expression by targeting its 3′ UTR and downregulation of miR‐99a‐5p accounted for TRIB2 hyperactivation and, subsequently, the promotion of CSC properties and radioresistance of ESCC cells. The gene discussed is TRIB2; the disease is esophageal squamous cell carcinoma.