Abstract: OBJECTIVE To investigate the changes of γ-interferon (IFN-γ), C-reactive protein (CRP), and neuron-specific enolase (NSE) of cerebrospinal fluid in patients with central nervous system infection, analyze their functions in the identification and diagnosis of infection in the central nervous system, so as to provide a theoretical basis for clinical diagnosis. METHODS A total of 78 cases of patients with central nervous system infection treated in the hospital from Aug. 2014 to Aug. 2015 were selected. According to the types of disease, they were divided into purulent meningitis group (22 cases), tuberculous meningitis group (26 cases), viral meningitis group (30 cases), and another 24 cases of non-CNS-infected patients were selected as control group. The IFN-γ content of NSE in CSF was determined by enzyme-linked immunosorbent assay (ELISA), and the difference of these three substances in all types of central nervous system infection were analyzed and compared. RESULTS The NSE content of cerebrospinal fluid in patients of purulent meningitis group, tuberculous meningitis group, and viral meningitis group were significantly higher than that of control group (P<0.05). The descending order of NSE content was viral meningitis group> tuberculous meningitis group> purulent meningitis group>control group, and the difference was significant (P<0.05). CONCLUSION During the diagnosis process of central nervous system infection, the combined determination of IFN-γ, content changes of cerebrospinal fluid CRP and NSE, can help to determine the extent of brain injury and identify the intracranial infection categories, it is worthy of clinical use.