We found that the expression of DHX38 in pancreatic ductal adenocarcinoma was reduced, which led to the retention of the fourth intron of RELL2 and the occurrence of nonsense-mediated mRNA decay, and ultimately inhibit the apoptosis of pancreatic cancer cells, and promote the occurrence of drug resistance in pancreatic cancer. The gene discussed is RELL2; the disease is familial pancreatic carcinoma.