Abstract: ObjectiveTo compare clinical characteristics and therapeutic outcomes between HIV and non-HIV patients with Cryptococcus neoformans meningitis (CNM). Methods A total of 73 patients with CNM (30 patients without HIV and 43 with HIV) were admitted from January 2012 to January 2017. The clinical manifestations, biochemical and microbiological characteristics of cerebrospinal fluid (CSF) were collected and analyzed. Results The patients in the two group displayed non-specific symptoms such as headache, fever, nausea and vomiting. Non-HIV CNM patients had more serious inflammatory reaction with higher karyocytes and protein level （P=0.000, P=0.041, respectively), while had lowere positive rate of primary ink staining in cerebrospinal fluid (70.0% vs. 93.0%, P=0.009), higher misdiagnosis rate (43.3% vs. 14.0%, P=0.005), longer hospitalization duration 〔(112.27±105.42) d vs. (52.64±39.17) d, P=0.021〕, higher adverse reactions rate of antifungal treatment was (80.0% vs. 30.2%, P=0.000). However, in HIV CNM patients, 40 (93.0%) patients did not receive antiviral therapy before and were diagnosed as AIDS for the first time; the therapeutic effect in this group was very poor with higher mortality (30.2% vs. 13.4%, P=0.000). Conclusion Immunity status should be considered in the diagnosis and treatment of CNM, since it is difficult to diagnose with long treatment period and poor prognosis.