Objective: To investigate the clinical features of neonatal hemophagocytic syndrome (HPCS) and improve the understanding of the disease. Methods: a case of hemophagocytic syndrome of premature infant with necrotizing enterocolitis was analyzed retrospectively. The keywords were "lymphohistiocytosis", "hemophagocytic syndrome", "newborn", "premature infant", "hemophagocytic lymphohistiocytosis", "prognosis", "neonatal" and "necrotizing enterocolitis", The clinical characteristics of HLH were summarized based on the diagnosis and treatment of this case. Results according to the diagnostic criteria of 2004 HLH, the diagnosis of HLH was clear. Necrotizing enterocolitis occurred in the course of hormone treatment. Hormone therapy was suspended until necrotizing enterocolitis was relieved. The patient was cured and discharged without intestinal perforation. Conclusion early diagnosis, early intervention and close monitoring are helpful to improve the prognosis. However, the treatment of HLH in preterm infants should be further explored.