Abstract: OBJECTIVE To investigate the influencing factors and the diagnostic value of serum levels of phosphatase and tensin homologous gene (PTEN) mRNA, interleukin (IL)-8 and intercellular adhesion molecule-1 (ICAM-1) in secondary infection from severe acute pancreatitis. METHODS A total of 426 patients with severe acute pancreatitis admitted to Jianyang City People's Hospital from Jun 2019 to Dec 2022 were retrospectively enrolled in the study. According to whether secondary infection occurred or not, they were divided into the infected group (181 cases) and the non-infected group (245 cases). The current status of secondary infection in patients with severe acute pancreatitis was counted. The risk factors for secondary infection in patients with severe acute pancreatitis were analyzed by univariate and multivariate analysis. Serum levels of PTEN mRNA, IL-8 and ICAM-1 were compared between the infected group and the non-infected group. The value of single and combined detection of serum PTEN mRNA, IL-8, ICAM-1 in the diagnosis of secondary infection from patients with severe acute pancreatitis was analyzed by receiver operating characteristic (ROC) curve. RESULTS Multivariate logistic analysis showed that fasting time >3 d, presence of mechanical ventilation, and high acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score were risk factors for secondary infection in patients with severe acute pancreatitis (P＜0.05). The serum PTEN mRNA level in the infected group was lower than that in the non-infected group, and the serum IL-8 and ICAM-1 levels were higher than those in the non-infected group (P＜0.05). The AUC value of serum PTEN mRNA, IL-8 and ICAM-1 combined detection in the diagnosis of secondary infection in patients with severe acute pancreatitis was higher than that of the individual detection (P＜0.05), and the sensitivity and specificity of combined detection were 86.19% and 92.24%, respectively, with higher diagnostic value. CONCLUSION The incidence of secondary infection was higher in patients with severe acute pancreatitis, and the influencing factors were fasting time, mechanical ventilation and APACHEⅡ score. The level of PTEN in patients with secondary infection from severe acute pancreatitis is low, and the levels of IL-8 and ICAM-1 are high. The combined detection of these indexes have high diagnostic value for the secondary infection in patients with severe acute pancreatitis, and can be used for early targeted prevention and treatment in clinical practice, reducing the risk of secondary infection from patients with severe acute pancreatitis.