Background：The clinical trend of EBV infected patients has been always the focus of attention. Case presentation： We report a rare case of chronic active EBV infection (CAEBV) with hemophagocytic lymphohistiocytosis progressed to childhood aggressive NK cell leukemia and cured by allogeneic hematopoietic stem cell transplantation. Conclusions: The EBV infection of T/NK cells can lead to CAEBV, and if the T/NK cells carry HLH related gene mutation, it is easy to accompany with the hemophagocytic syndrome, and this type of CAEBV may rapidly progress to ANKL or other neoplastic diseases. Therefore, we should reinforce the knowledge on this kind of patients to receive appropriate and timely treatment.