Objective: Through the analysis and summary of the clinical features of neurosyphilis, this study aims to give references for reducing the clinical misdiagnosis of neurosyphilis. Methods: A retrospective analysis of the clinical data of 24 cases of neurosyphilis in Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to January 2017 was conducted. Results: Of 24 cases of neurosyphilis, 21 cases were males, 3 were females; the median age was 55 years (range: 28 to 75 years); 3 cases had the first clinical manifestation of epilepsy, 3 cases had paralytic dementia, 5 cases had cerebral vascular disease-like attack, and 5 cases had spinal cord symptoms. Twenty-four cases had positive results of serum treponema pallidum particle agglutination test (TPPA) and toluidine red unheated serum test (TRUST) as well as cerebrospinal fluid TPPA. There were 21 cases had abnormal count of cerebrospinal fluid cells and 20 cases had increased protein content. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) showed 10 cases had lacunar infarction, 3 cases had acute cerebral infarction, 1 case had cerebral hemorrhage, 5 cases had vascular stenosis, thinning and absence, 1 case had nucleus abnormal signal, 1 case had spinal cord infectious granuloma, 1 case had spinal cord abnormal signal, 2 cases had brain lobe abnormal signal, 2 cases had brain atrophy and hippocampal atrophy, and 4 cases had no abnormal intracranial findings. All the patients received penicillin treatment immediately after the diagnosis of neurosyphilis was confirmed, and the symptoms were relieved after treatment. Conclusion: Combination of clinical manifestations with laboratory and imaging could help to reduce the misdiagnosis of neurosyphilis.