In this study, we provide a novel notion that PRMT5 induces the phosphorylation of EGFR, and then activates phosphorylation of Akt and its downstream GSK3β, and thereby up‐regulates expression of β‐catenin to enhance the migratory and invasive motility and promotes EMT of pancreatic cancer cells. Here, PRMT5 is linked to pancreatic neoplasm.