Objective To investigate the application of cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) in the diagnosis of intracranial bacterial infection after pediatric neurosurgery. Methods Clinical data of patients who met the diagnostic criteria for intracranial bacterial infection (including clinical diagnosis and confirmed diagnosis) after neurosurgery in the pediatric intensive care unit of a hospital of Central South University from January 1, 2020 to August 31, 2023 were analyzed. From October 2021, CSF culture and mNGS detection were performed before empirical use of anti-intracranial infection agents, for patients with negative mNGS results of CSF, combined with CSF culture results and clinical data, the empirical anti-intracranial infection treatment was not given or stopped as early as possible, and follow-up was conducted. Results A total of 43 children were included in the analysis, including 38 cases in clinical diagnosis group and 5 cases in pathogen diagnosis group. There were no statistically significant differences in routine and biochemical indicators of CSF detection between the two groups (both P>0.05). Among 38 cases in the clinical diagnosis group, 10 clinically diagnosed cases (control group) received empirical antimicrobial treatment after clinically diagnosed intracranial infection from January 2020 to September 2021; 28 clinically diagnosed cases of intracranial infection had negative results of mNGS pathogen and cerebrospinal fluid culture from October 2021 to August 2023 (intervention group). Sixteen cases didn't receive empirical anti-intracranial infection treatment, and the other 12 cases stopped the empirical anti-intracranial infection treatment in time after the reporting of negative mNGS and combining with clinical data. No bacterial meningitis occurred among the 28 cases during the followed-up, and the average duration (0[0, 4] days) of intracranial antimicrobial use was shorter than that of the 10 clinically diagnosed cases in the control group (8[7, 11] days, P < 0.05). Conclusion CSF mNGS can improve the pathogen detection rate of intracranial bacterial infection after neurosurgery, and the detection result of mNGS can help guide the rational use of antimicrobial agents in the clinically diagnosed intracranial bacterial infection after neurosurgery.