〔Abstract〕 Objective To investigate the influence of etiology and clinical features on prognosis of adult hemophagocytic lymphohistiocytosis(HLH). Methods The clinical data of 104 adult HLH patients diagnosed in 5 medical centers of Huaihai Lymphoma Working Group(HHLWG). MaxStat algorithm was used to determine the optimal cut-off values of continuous variables. Cox proportional hazard model was used for univariate and multivariate analysis on prognosis; the survival curve was drawn by Kaplan-Meier; the differences between groups were tested by Log-rank test. Results Among the 104 HLH patients, 52 cases(50%) were male, with a median survival time of 2.13 months. The most common etiology in 104 patients was EBV infection(35.7%), followed by lymphoma(18.2%). The optimal cut-off values of age, fibrinogen, platelet, triglyceride, albumin and serum creatinine by MaxStat algorithm were 50-y, 2.27 g/L, 150×109/L, 2.87 mmol/L, 30.3 g/L and 56 μmol/L respectively. The overall survival(OS) rates of HLH due to different etiologies were different, among which the overall survival rates of lymphoma associated hemophagocytic syndrome(LAHS) and EBV-HLH patients were 15.8% and 30.2%, respectively. Multivariate analysis showed that age, albumin, serum creatinine and fibrinogen were independent prognosis factors for adult HLH. Conclusion EBV infection is the common cause of adult HLH. Among the different cause of HLH, the patients with LAHS have the lowest OS and the worst prognosis.