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. This evidence concerns the gene DHX38 and familial pancreatic carcinoma.