Purpose: To investigate the clinical characteristics of nasopharyngeal carcinoma (NPC) and a concomitant hepatitis B virus (HBV) infection, as well as the potential effects of HBV infection and antiviral therapy on prognosis. Methods: We conducted a retrospective chart review of all NPC patients from December 2010 to December 2014. After collecting medical records and conducting follow-ups on patients, a total of 876 eligible NPC patients were included. For each patient, medical records were reviewed. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis. Results: Among the 876 participants, 106 (12.1%) patients were HBV-infected patients. The hepatitis B surface antigen-positive [HBsAg(+)] group had a lower CD 4+ T cell count than the HBsAg(−) group (P = .048). Among patients with stage I/II NPC, 5-year overall survival (OS), disease-free survival (DFS), relapse-free survival, and distant metastasis-free survival (DMFS) of the HBsAg(+) group were 82.5%, 70.7%, 87.7%, and 76.6%, respectively, whereas those of the HBsAg(−) group were 91.4%, 86.0%, 93.8%, and 92.1%, respectively. Statistically significant differences in OS, DFS, and DMFS existed between both groups (P = .017, .018, and .004, respectively). The multivariate analysis indicated that HBsAg status and N stage are independent risk factors affecting OS, DFS, and DMFS of NPC patients. A statistically significant difference in 5-year DMFS existed between the antivirus (90.0%) and no-antivirus groups (70.0%) (P = .043). Conclusions: Hepatitis B virus infection is an independent risk factor for early stage NPC, which may be associated with its reduced immune functions compared to the HBsAg(−) group. Anti-HBV treatment may improve the prognosis of HBV-infected NPC patients. K E Y W O R D S antiviral therapy, hepatitis B virus, nasopharyngeal carcinoma, prognosis 542 | WENG Et al.