OBJECTIVE To study the main factors influencing prognosis of hemophagocytic lymphohistiocytosis (HLH) in children by summarizing the clinical features of HLH and investigating the relationship between relevant factors and prognosis. METHODS The medical data of 63 children with HLH were retrospectively reviewed. Kaplan-Meier method was employed to draw survival curves. Factors influencing prognosis were assessed with Cox univariate analysis, and Cox multivariate analysis was done on statistically significant factors. RESULTS The 3-year and 5-year survival rates were both 62.9%. The survival rate decreased from 98.4% at 1 day after definite diagnosis to 73.2% at 4 months. Univariate analysis demonstrated only one factor, which was that the condition of platelet recovery after treatment of 2 to 3 weeks was significantly related to prognosis (P=0.002). In children receiving etoposide therapy, temperature recovery after one day of treatment was significantly related to prognosis (P=0.016). CONCLUSIONS Children with HLH have a satisfactory prognosis, but the survival rate reduces rapidly in the first 4 months after definite diagnosis. Platelet recovery after treatment of 2 to 3 weeks and temperature recovery after one day of treatment are factors influencing prognosis of HLH in children.