In this study, we screened HSPB1 as an exosomal protein regulator for ferroptosis of pancreatic cancer cells, and pancreatic cancer cell‐derived 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. Here, HSPB1 is linked to pancreatic neoplasm.