Abstract: Objective To study the relationship between serum cystatin C (Cys C) level and clinical features in patients with neurosyphilis, and evaluate its clinical significance. Methods We collected 30 patients as neurosyphilis group, 30 patients as syphilis (non-neurosyphilis, N-NS) group and 20 healthy as control group between September 2016 and May 2018. The levels of serum Cys C were tested by using immunology turbidimetric method. The clinical and laboratory characteristics were compared among the three groups. Results The patients with neurosyphilis had higher serum Cystatin C levels as compared with the patients with syphilis and healthy control (P＜0.05); however， no significant difference between the N-NS and control group (P>0.05). Serum Cystatin C level was significantly decreased in neurosyphilis group after the antisyphilitic treatment (P<0.05). The mean ROC-plot AUC for Cys C was 0.71 [P=0.022, 95% CI(0.53，0.89)]. The optimal threshold value for Cys C was 1.09 mg/L with the sensitivity of 55% and specificity of 90%. The correlation analysis showed that the serum Cys C levels were positively associated with CSF protein levels and MMSE score (r=0.232, P=0.012; r=0.273, P=0.003), but not associated significantly with RPR titer, CSF cell count and CSF pressure (r=0.413, P=0.154; r=0.313, P=0.446; r=-0.124, P=0.142) in patients with neurosyphilis. Conclusion The levels of serum Cys C is significantly associate with neurosyphilis. To test the levels of Cys C can evaluate the severity of the disease and predict the risk of getting neurosyphilis.