Objective：To investigate the clinical characteristics and outcomes of central nervous system（CNS） involvement in pediatric patients with hemophagocytic syndrome，also known as hemophagocytic lymphohistiocytosis（HLH）. Methods：A total of 112 pediatric patient who were newly diagnosed with HLH at the Children’s Hospital Affiliated to Nanjing Medical University during November 2008 to December 2017 were retrospectively evaluated for CNS involvement. Neurological symptoms，cerebrospinal fluid（CSF） findings，neuroradiological results and treatment outcome were analyzed. Results：About 84.1% patients（22/29）with CNS-HLH in our study had neurologic manifestation. The most two common symptoms were seizures and disturbance of consciousness. CSF analysis and neuroradiological studies were performed in 28 patients. The results showed that 18 patients（62.0%）had CSF abnormalities，9 patients（32.1%）presented nodular or diffuse signal abnormalities，while 17 patients（60.7%）had cerebral atrophy，mild ventriculomegaly or other signs of chronic changes. Five-year cumulative survival rate of 112 patients with HLH was 75.9%. Patients with CNS involvement showed poor overall survival compared to those without CNS involvement（χ2=3.936，P=0.047）. Overall survival of CNS-HLH who did not receive intrathecal therapy was inferior to those who received intrathecal therapy（χ2=6.003，P=0.014）. Cox multivariate analysis showed that absence of intrathecal therapy and severe anemia（Hb≤60 g/L）at diagnosis were independent risk factors in pediatric CNS-HLH. Conclusion：CNS involvement is associated with poor prognosis in pediatric patients with HLH. Children with HLH require overall assessment of neurological involvement and appropriate therapy. Lack of intrathecal therapy and severe anemia are related to poor prognosis.