Mechanistically, we demonstrated that the decrease in N6-methyladenosine (m6A)-modified RNA catalyzed by the m6A demethylase AlkB Homolog 5, RNA Demethylase (ALKBH5) induced the upregulation of CASC8, which subsequently promoted ESCC progression through the post-translational upregulation of hnRNPL. Here, HNRNPL is linked to esophageal squamous cell carcinoma.