Objective To study the impact of neurosurgical central nervous system infection (NCNSI) after neurosurgical operation on post-operative hospitalization expense and length of hospital stay, and provide health economic support for infection prevention and control. Methods Clinical data of patients who underwent neurosurgical operation in a tertiary first-class comprehensive hospital in Shanghai from January 1, 2015 to December 31, 2020 were retrospectively collected. According to whether NCNSI occurred after operation, patients were divided into infection group and non-infection group, database of covariate equilibrium was constructed with 1 ∶1 propensity score matching method, post-operative expenses and length of hospital stay of two groups of matched patients were compared. Results A total of 1 661 patients after neurosurgical operation were included, 83 of whom developed NCNSI, with an incidence of 5.00%, 77 pairs of propensity scores were matched successfully. After matching, the median of total hospitalization expenses in patients in infection group and non-infection group were 96 487 Yuan and 44 691 Yuan respectively, direct economic loss was 51 796 Yuan; the median length of hospital stay was 27 days and 10 days respectively, and infection group was extended for additional 17 days. Conclusion NCNSI in neurosurgery patients prolongs length of hospital stay and increases hospitalization expenses, propensity score matching method can provide more accurate results for the economic burden research.