Objective To determine the cerebrospinal fluid/serum albumin ratio (QALB) in patients with neurosyphilis, and to explore the correlation between the blood-brain barrier permeability and the cognitive impairment. Methods A retrospective study was conducted on the clinical data from 93 patients with anti-human immunodeficiency virus (HIV)-negative neurosyphilis diagnosed by Changhai Hospital of Naval Medical University (Second Military Medical University) from Jan. 2010 to Jan. 2018. According to the mini-mental state examination (MMSE) score, the patients were divided into cognitive dysfunction group (n=38) and non-cognitive dysfunction group (n=55), and the demographic data, clinical data and cerebrospinal fluid biochemical data were compared between the two groups. Pearson bivariate correlation analysis was used to analyze the relationship between blood-brain barrier permeability and cognitive dysfunction in neurosyphilis patients. Results There were no significant differences in gender, age, education level, marital status, cerebrospinal fluid leukocyte count, cerebrospinal fluid protein, immunoglobulin G (IgG), IgG index, 24-h intrathecal IgG synthesis, or oligoclonal band between the cognitive dysfunction group and non-cognitive dysfunction group (all P>0.05). The QALB was significantly higher in the cognitive dysfunction group than that in the non-cognitive dysfunction group ([16.42±9.24]×10^-3 vs[3.60±1.11]×10^-3, t=10.907, P<0.01). The incidence of cognitive dysfunction was significantly higher in the elevated QALB (> 7×10^-3) patients versus the normal QALB (≤ 7×10^-3) patients (92.11%[35/38] vs 67.27%[37/55], χ²=7.927, P=0.002). Pearson bivariate correlation analysis showed that QALB was negatively correlated with MMSE score (r=-0.410, P=0.024). Conclusion The neurosyphilis patients with blood-brain barrier damage are prone to cognitive dysfunction, and the higher the blood-brain barrier permeability, the more serious the cognitive dysfunction. Monitoring the permeability of blood-brain barrier can contribute to the assessment of intelligent damage in patients with neurosyphilis.