Abstract: Objective To explore the value of serum and cerebrospinal fluid(CSF) neuron specific enolase(NSE), S100 protein and procalcitonin(PCT) in differential diagnosis between tuberculous meningitis and viral encephalitis. Methods A total of 44 tuberculous meningitis patients and 45 viral encephalitis patients hospitalized in the Department of Neurology, Zhengzhou First People's Hospital from January 2016 to July 2018 were selected. The severity of the disease and treatment changes was evaluated by the Central Nervous System(CNS) Infection Severity Score Scale. ELISA and electrochemiluminescence immunoassay were used to determine the levels of NSE, S100 protein and PCT in serum and cerebrospinal fluid. The levels of NSE, S100 protein and PCT in patients with tuberculous meningitis were dynamically observed before and after the treatment, and their changes and diagnostic efficacy before and after the treatment were compared among the three groups. Results The patients with moderate and severe lesions in tuberculous meningitis group were significantly more than those in viral encephalitis group(P<0.05). After the treatment, the levels of NSE, S100 protein and PCT in serum and cerebrospinal fluid of patients with tuberculous meningitis were significantly lower than those before the treatment(all P<0.05). The levels of NSE, S100 protein and PCT in serum and cerebrospinal fluid of patients with viral encephalitis were significantly lower than those of patients with tuberculous meningitis(all P<0.05). The levels of NSE, S100 protein and PCT in serum and cerebrospinal fluid had a high diagnostic value in the differential diagnosis of encephalitis vulgaris. Conclusion By comparing the levels of NSE, S100 protein and PCT in serum and cerebrospinal fluid of patients with encephalitis vulgaris, it was found that the changes of NSE, S100 protein and PCT level are consistent with the severity score of CNS infection, which can well reflect the severity and treatment changes of craniocerebral injury, and be helpful to the early differential diagnosis between tuberculosis and encephalopathy.