METTL14/miR‐99a‐5p/TRIB2 constitutes a positive feedback loop that enhances CSC properties and radioresistance of ESCC cells through inducing HDAC2‐mediated p21 epigenetic repression dependent on Akt/mTOR/S6K1 pathway. Here, METTL14 is linked to esophageal squamous cell carcinoma.