BACKGROUND Malaria-associated secondary hemophagocytic lymphohistiocytosis (HLH) is rare. Moreover, the literature on malaria-associated HLH is sparse, and there are no similar cases reported in China. CASE SUMMARY We report the case of a 29-year-old woman with unexplained intermittent fever who was admitted to our hospital due to an unclear diagnosis. The patient concealed her history of travel to Nigeria before onset. We made a diagnosis of malaria-associated secondary HLH. The treatment strategy for this patient included treatment of the inciting factor (artemether for 9 d followed by artemisinin for 5 d), the use of immunosuppressants (steroids, intravenous immunoglobulin) and supportive care. The patient was discharged in normal physical condition after 25 d of intensive care. No relapses were documented on follow-up at six months and 1 year. CONCLUSION Early diagnosis of the primary disease along with timely intervention and a multidisciplinary approach can help patients achieve a satisfactory outcome.