Objective To study the economic burden caused by healthcare-associated infection (HAI) in patients with severe acute pancreatitis (SAP), and provide theoretical basis for formulating HAI prevention and control measures. Methods Patients with SAP discharged from a tertiary first-class hospital in Jiangxi Province from July 1, 2023 to June 30, 2024 were selected as the study subjects. Information including demographic characteristics, clinical data, and hospitalization expense were collected. Patients were divided into a HAI group and a non-HAI group according to HAI occurrence. A propensity score matching (PSM) method was used to conduct a 1 ∶2 ma-tching, and differences in the length of hospital stay and hospitalization expense between the two groups of patients after PSM were compared. Results A total of 709 patients were included in the analysis, out of which 65 cases experienced HAI, with a HAI incidence of 9.17%. After PSM, all 65 patients in the HAI group were successfully matched. The length of hospital stay, total hospitalization expense, expenses of medication and hygiene product of patients in the HAI group were all higher than those in the non-HAI group, and differences were all statistically significant (all P<0.001). Patients who experienced ≥2 episodes of HAI had a higher economic burden than those who experienced only once (P<0.05). HAI of bloodstream, abdomen, digestive system, and respiratory system significantly increased the economic burden of patients (all P<0.05). Conclusion HAI in SAP patients can extend the length of hospital stay and increase economic burden of patients. Targeted infection prevention and control mea-sures should be formulated to reduce the incidence of HAI and save medical resources.