Abstract: The development of neurosyphilis may be associated with Treponema pallidum neuroinvasion and host immunity. Human immunodeficiency virus (HIV) infection may increase the incidence of neurosyphilis. Cerebrospinal fluid (CSF)-rapid plasma reagent (RPR) test can be applied as a substitute for venereal disease research laboratory test (VDRL) to the diagnosis of neurosyphilis. Detection of tau protein and chemokine CXCL13 in CSF also has great value in the diagnosis of neurosyphilis. For patients allergic to penicillin, doxycycline or ceftriaxone may serve as alternative drugs. Adjuvant therapy may benefit the improvement of syphilis symptoms and strengthen the efficacy of antisyphilitic treatment. Dynamic observation of serum RPR titer can be used to monitor the treatment efficacy in patients with neurosyphilis.