Chronic active Epstein-Barr virus (CAEBV) infection is a complex and heterogeneous disease with features of both immunodeficiency and malignant neoplasms. 10 patients aged 14～62 years with confirmed CAEBV infection were collected. The clinical features included splenomegaly(10/10), hepatomegaly(9/10), abnormal liver function(9/10) and CD8+T lymphopenia(3/3). Whole exon sequencing of peripheral blood showed a total of 410 immune genes were screened in 10 patients. They were primarily enriched in ‘Human papillomavirus infection’ and ‘Complement and coagulation cascades’. HE also showed lymphocytic infiltration in liver tissue of the CAEBV group. Immunohistochemistry showed the positive score of CD8+ T cells in the CAEBV patients was higher than that of controls (p<0.05). But there was no significant difference between the two groups in terms of other immune cells (p>0.05). Based on the findings, we further investigated the CD8+ T lymphocyte-related hepatitis pathogenesis caused by CAEBV infection. Granzyme B and perforin in liver tissue showed no significant difference between the two groups (p>0.05). Fas, FasL and Caspase-8, were a higher expression in CAEBV patients than controls (p<0.05). C1q of liver sinusoidal endothelial cells (LSECs) and Glisson’s capsule (GC), as well as C3d of LSECs, were a higher expression in CAEBV patients than controls both (p<0.05). C4d of LSECs and GC and C3d of GC showed no significant difference between the two groups (p>0.05). Therefore, Fas/FasL and complement may involve the immune-related mechanism in CAEBV infection.