Objective:To retrospectively analyze the clinical characteristics and prognostic risk factors of EBV-associated hemophagocytic syndrome based on multicenter data.Methods:A total of 132 patients with EBV-HLH from 9 medical centers in Huaihai Lymphoma Working Group from January 2013 to August 2020 were selected and their clinicopathological data were collected. The optimal cut-off point of EBV-DNA copy number was calculated using restricted cubic spline. Cox proportional hazards model was used for univariate and multivariate analysis. Kaplan-Meier curves of patients were drawn. Log-rank test was used for comparison between groups. Results:The median age of 132 patients was 25 years old,including 61 children(< 14 years old)(46.21%),25 elderly patients(≥60 years old)(18.94%),124 patients(93.94%)with fever,and 116 patients(87.88%)with elevated serum ferritin. The prognosis of children patients was better than that of adults(P < 0.001),and the six -month cumulative survival rates of the two groups were 90.2% and 38.0%,respectively. The percentage of albumin,serum triglyceride,alanine aminotransferase and lymphocyte in the children group was higher than that in the adult group,while the serum creatinine was lower than that in the adult group. The age and serum creatinine of the survival group were lower than those of the death group,while the levels of serum triglyceride were higher than those of the death group(P < 0.05). Multivariable analysis showed that age and EBV-DNA copy number were independent risk factors for survival outcome of EBV-HLH patients. Conclusion:The early mortality of EBV-HLH is high and the prognosis is poor. The EBV-DNA copy number and age at initial diagnosis are the adverse factors affecting the prognosis of EBV-HLH patients.