The clinical data of 4 patients with atypical neurosyphilis (NS) mimicking viral encephalitis (VE) admitted to Beijing Ditan Hospital from July 2015 to January 2020 were retrospectively analyzed. All the 4 patients were males with an average age of (43±8) years. The patients manifested with mental and behavior disorders and cognitive impairment. Three patients had epilepsy and 1 patient had fever. The treponemal pallidum particle agglutination (TPPA) , fluorescent treponemal antibody-absorption test (FTA-ABS) -IgG and toluidine red unheated serum test (TRUST) were all positive in blood and the cerebral spinal fluid (CSF) , and white blood cell count and protein level in CSF were all evaluated. The head MRIs were all abnormal, 3 of which showed hyperintensity in fluid attenuated inversion recovery (FLAIR) and T2-weighted image located in limbic system and 1 showed hyperintensity in the bilateral cortex and the subcortical areas. All patients improved evidently and the lesions became smaller after penicillin treatment. Atypical NS mimicking VE is rare, and at early diagnosis and timely treatments can contribute to a good clinical prognosis.