Numerous animal experiments have implicated ferroptosis in the pathogenesis of acute pancreatitis (AP). Nonetheless, due to sampling constraints, the precise role of ferroptosis in the human body during AP remains elusive. Method: Peripheral blood sequencing data of patients with acute pancreatitis (GSE194331) were obtained from the Gene Expression Omnibus (GEO) database. We analyzed differentially expressed genes whose expression increased or decreased with increasing disease severity and intersected them with the ferroptosis gene set to identify ferroptosis-related driver genes for the disease. The hub genes were selected using machine learning algorithms, and a nomogram diagnosis model was constructed. Clinical samples, animal models, and an in vitro experiment were also used for validation. The investigation unveiled 22 ferroptosis-related driver genes, and we identified three hub genes,