Objective To analyze the clinical characteristics of patients with acquired immunodeficiency syndrome(AIDS) and central nervous system (CNS) Talaromyces marneffei (T. marneffei) infection, and improve early clinical diagnosis level. Methods Clinical data of 5 AIDS patients who were co-infected with T. marneffei confirmed by cerebrospinal fluid (CSF) culture and admitted to the Fourth Peoples' Hospital of Nanning City from 2014 to 2020 were analyzed retrospectively. Results Among the 5 AIDS patients complicated with CNS T. marneffei infection, 4 were male, with an average age of 35.2 years. The average time for isolating T. marneffei in CSF was 8 days. CSF changes mainly manifested as an increase in white blood cell count and protein, as well as a decrease in glucose and chloride levels. The main manifestation of cranial imaging examination was intracranial infection. Five patients all died, 2 of whom were misdiagnosed as central nervous Mycobacterium tuberculosis infection, 2 critically ill patients died within 1 week after admission, and 1 patient received effective antifungal treatment but ultimately died due to septic shock. Three patients previously received standardized anti-human immunodeficiency virus treatment. Conclusion AIDS complicated with CNS T. marneffei infection lacks specific clinical manifestations. Early diagnosis is difficult, misdiagnosis and missed diagnosis during clinical practice occur often, and it is with high mortality. Clinicians should attach great importance to it.