To summarize and analyze the neurological manifestations, biochemical and imaging characteristics, treatment methods, and prognosis of patients with central nervous system-hemophagocytic lymphohistiocytosis (CNS-HLH), so as to deepen the clinical understanding of this disease. Methods: A retrospective analysis was conducted on the clinical data of 33 CNS-HLH patients treated at Beijing Friendship Hospital, Capital Medical University, from January 2022 to December 2024. Additionally, the PubMed database was searched for literature reports of 484 CNS-HLH patients published from January 2020 to December 2025. Descriptive statistical analysis was performed on the etiology, clinical manifestations, laboratory and imaging examinations, treatment regimens, and prognosis of the two patient groups. Results: Among the 33 patients from our hospital, the main etiologies were Epstein-Barr virus (EBV) infection (51.5%) and lymphoma (24.2% ). The primary neurological manifestations were alterations in consciousness/mental status (24.2% ) and focal neurological deficits (24.2% ). Cerebrospinal fluid (CSF) examinations most commonly showed elevated pressure (75.8%) and elevated protein levels (60.6%), while the abnormality rate on cranial MRI was 63.3%. In terms of treatment, 87.9% of patients received intrathecal injection, and 51.5% underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a 1-year survival rate of 75.8%. Among the 484 patients reviewed from the literature, the main etiologies were EBV infection (64.9%) and familial genetic defects (50.2% ). Clinical manifestations were predominantly epilepsy (58% ) and disturbance of consciousness (39% ). The CSF abnormality rate was 83.3%, and the cranial MRI abnormality rate reached 85.6% , with lesions most frequently involving the cerebral hemispheres (74.4% ). Regarding treatment, 58% received intrathecal injection, while only 8% underwent allo-HSCT, and the overall mortality rate was 46.3% . Conclusion: The etiology of CNS-HLH is predominantly EBV infection and hereditary immunodeficiency, and its neurological manifestations lack specificity. Biochemical abnormalities in CSF and characteristic changes on cranial MRI are crucial for diagnosis. Early combined immunosuppression, targeted therapy, and intrathecal injection are helpful for controlling the disease. Allogeneic hematopoietic stem cell transplantation is an important means to improve prognosis; however, the overall mortality rate remains high, warranting high clinical vigilance.