A retrospective analysis of the etiology, clinical manifestations, laboratory test indices, treatment options and clinical regression of 72 patients with HPS in a multicenter was performed. Results The primary diseases of 72 patients were mostly viral infection and T-cell lymphoma. The main clinical manifestations were persistent high fever (100%) and splenomegaly (83.3%) most frequently. Fever (100%), reduced peripheral blood levels of two or more blood lines (97.2%), increased serum soluble IL-2 receptor (sCD25) levels (93.1%) and reduced NK cell activity (94.4%) were found to be more sensitive in the diagnosis. Laboratory tests revealed that the percentage of serum glycated ferritin in the HPS patient group was (174±160)%. It was significantly lower than the (53.6±13.3)% of normal controls. Serum TNF-a levels were (143.24-64.8) pg/L, significantly higher than those of normal controls (66.9 4-194) pg/L. Most patients with HPS had hepatic impairment (83.6%), with predominantly elevated AST and hypoalbuminemia. 47 patients with treated HPS had an overall survival rate of 46.8% at 15 weeks. Among them, 27 patients with fludarabine combined with high-dose hormone therapy for HPS had an overall survival rate of 63.O%. The platelet count and fibrinogen levels were significantly lower in the death group than in the survival group (P<0.01). Conclusion HPS can be caused by a variety of etiologies and has a diverse clinical presentation. Fever, peripheral blood hypocellularity of two or more blood lines, elevated serum sCD25 levels, and reduced NK cell activity are more sensitive in the diagnosis. Changes in glycated ferritin percentage, serum TNF-a levels help in the diagnosis of HPS. fludarabine combined with high-dose hormones is an effective treatment option. Decreased platelet count and fibrinogen levels are poor prognostic factors for the disease.