BACKGROUND Chronic active Epstein-Barr virus infection ( EBV) is a systemic EBV-positive lymphoproliferative disease, which may lead to fatal illness. There is currently no standard treatment regimen for chronic active EBV (CAEBV), and hematopoietic stem cell transplantation is the only effective treatment. We here report a CAEBV patient treated with PEG-aspargase, who achieved negative EBV-DNA. CASE SUMMARY A 33-year-old female Chinese patient who had fever for approximately 3 mo was admitted to our hospital in December 2017. EBV-DNA was positive with a high copy number. She was diagnosed with chronic active EB virus infection. PEG-aspargase was administered at a dose of 1500 U/m(2) at a 14-d interval, resulting in eradication of EBV for more than 6 mo. The effect of PEG-aspargase in this patient was excellent. CONCLUSION A chemotherapy regimen containing PEG- aspargase for CAEBV may be further considered.