Taken together, our data demonstrate that RPS15 could promote the translation of MAPK14 and MKK6 mRNA, which were directly bound and recognized in an m6A dependent manner by the KH3-4 domain of IGF2BP1, which then enhanced p38 and MKK6 TE and promoted the proliferation and metastasis of ESCC cells. This evidence concerns the gene MAP2K6 and esophageal squamous cell carcinoma.