Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is a rare syndrome characterized by prolonged infectious with elevated peripheral blood EBV DNA load. CAEBV has been primarily reported in East Asia. Aggressive NK cell leukemia (ANKL) is a rare malignant lymphoproliferative disorder of mature NK cells closely associated with Epstein-Barr virus (EBV). The morphology of ANKL tumor cells, highly atypical features with basophilic cytoplasm containing azurophilc granules, with a median survival of less than three months. A 9-year-old boy with CAEBV infection for more than three years with EBV-associated encephalitis received an allogeneic hematopoietic stem cell transplant four months ago. His health rapidly deteriorated with pancytopenia, diffuse intravascular coagulation, central nervous system and liver dysfunction. Monoclonal NK cells appeared in the bone marrow and cytokine IL-10 was significantly increased. His NK cells had an abnormal immune phenotype and morphological abnormality. This patient had clinical progressed of CAEBV to ANKL, while clinical progression was rapid and fatal.