In conclusion, we screened HSPB1 as an exosomal protein regulator for ferroptosis of pancreatic cancer cells, and exosomal HSPB1 played a promoting role in pancreatic cancer progression by interacting with the RNA binding protein FUS and suppressing FUS/NRF2/HO‐1/P450‐mediated ferroptosis. This evidence concerns the gene HMOX1 and familial pancreatic carcinoma.