Objective To investigate the epidemiological characteristics and disease burden of hospital-acquired influenza. Methods Medical records of inpatients admitted to West China Hospital, Sichuan University from 2020 to 2023 were retrospectively collected to analyze the three-distribution (temporal, spatial and population). Propensity score matching combined with generalized linear model were adopted to compare the differences in length of hospital stay and various medical expenses between the hospital-acquired influenza group and the control group, so as to explore the impacts of hospital-acquired influenza on the length of hospital stay and medical costs of inpatients. Results A total of 970 366 hospitalized patients were included, among whom 588 hospitalized influenza cases were enrolled, including 175 cases of hospital-acquired influenza and 413 cases of community-acquired influenza. A control group of 175 cases was matched using propensity score matching. The hospitalization duration [19.00 (13.00, 35.00) vs. 10.00 (6.00, 16.50) days, P<0.001] and total medical expenses [34 764.13 (17 851.96, 110 687.64) vs. 14 769.48 (8 028.96, 37 123.71) yuan, P<0.001] of hospital-acquired influenza patients were higher than those of the control group. The results of the generalized linear models showed that hospital-acquired influenza could prolong hospitalization duration (P<0.001) and increase total hospitalization costs (P<0.001). Conclusions Hospital-acquired influenza significantly prolongs the length of hospital stay and increases medical expenditures of inpatients, which greatly aggravates the disease burden of patients and medical institutions. Therefore, medical institutions should attach importance to the prevention and control of influenza virus in hospitals to reduce the incidence of hospital-acquired influenza.