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This study aimed to investigate the relationship between clinical features and prognosis of adult secondary hemophagocytic syndrome (HPS).A retrospective analysis was conducted on the pathogenesis, clinical manifestations, laboratory examinations, treatment options, and prognosis of 47 patients with adult secondary HPS diagnosed from January 2013 to December 2015.The average age at disease onset was (46.26 ± 18.98) years with a male:female ratio of 1:1.14. Thirteen patients died, with the highest mortality rate in patients with HPS underlying blood system malignancy (33.33%, 2/6). The mortality rate in patients with HPS underlying autoimmune disorders was the lowest (18.75%, 3/16). The Kaplan–Meier analysis indicated that signs of hemorrhage, pulmonary and nervous system involvement, serous effusion, and decrease in the blood platelet count were associated with death. The Cox regression analysis revealed that signs of hemorrhage, pulmonary involvement, serous effusion, and nervous system involvement were independent risk factors of patient death.Adult secondary HPS has multiple etiologies and diversified clinical features. The risk of death increases in patients with signs of hemorrhage, serous effusion, pulmonary involvement, and nervous system involvement.