Objective: This study was designed to investigate the expression of serum autophagy-related protein P62 in patients with severe acute pancreatitis (AP) and its correlation with prognosis. Methods: Eighty patients with AP treated in the First Affiliated Hospital of Gannan Medical University from January 2020 to January 2021 were enrolled as study subjects in this retrospective analysis, and they were placed into the mild AP group (n=52) or the severe AP group (n=28). According to clinical outcomes, these 80 patients were divided into a good prognosis group (GP group, n=51, surviving without serious complications such as organ failure) and a poor prognosis group (PP group, n=29, death or developing organ failure). The differences in C-reactive protein (CRP), P62 and the Acute Physiology and Chronic Health Evaluation II (APACHE-II) were compared upon admission. The changes of CRP, P62 and APACHE-II within 1-7 h after admission were dynamically analyzed in the two groups. Spearman correlation analysis was performed to explore the correlation between P62 and APACHE-II scores, and the receiver operating characteristic (ROC) curve of P62 related to poor AP outcome was plotted. Results: CRP, P62 and APACHE-II in the mild AP group were significantly higher than those in the severe AP group, and these in the PP group were also significantly higher than those in the GP group (P