Background: Both nasopharyngeal carcinoma (NPC) and hepatitis B virus (HBV) infection are prevalent in southern China.Recently, HBV-infected patients with diffuse large B-cell lymphoma or multiple myeloma were found to have distinct clinical characteristics and/or outcomes compared to uninfected patients.However, the clinical features of patients with NPC and chronic HBV infection have not been elucidated.Thus, we investigated the prevalence and prognostic value of chronic HBV infection in patients with NPC in southern China.Methods: A total of 1301 patients with non-metastatic NPC treated at the Sun Yat-sen University Cancer Center between 2003 and 2007 were retrospectively reviewed.Chronic HBV infection was defined as hepatitis B surface antigen (HBsAg)-seropositivity.All patients were restaged according to the 7th edition of AJCC NPC staging system.Results: In this series, 10.9% (142/1301) of patients had chronic HBV infection.The proportion of non-cancer related deaths (15.0% vs.12.1%, P=0.618)and severe hepatic adverse events (3.5% vs.0.9%;P=0.145) were similar in HBV-infected and uninfected patients with NPC.The 5-year overall survival (OS), progression-free survival (PFS), and locoregional relapse-free survival (LRFS) rates for HBV-infected and uninfected patients with NPC were 70.9% and 80.8% (P=0.003),63.7% and 73.0% (P=0.016), and 81.7% and 88.2% (P=0.035), respectively.Multivariate analysis identified chronic HBV infection as an independent unfavorable prognostic factor inNPC for OS (HR 1.684, 95% CI 1.198-2.366;P =0.003), PFS (HR 1.451, 95% CI 1.076-1.955;P =0.015) and LRFS (HR 1.573, 95% CI 1.005-2.463;P =0.048).Conclusion: This study demonstrates that chronic HBV infection is an independent prognostic factor associated with unfavorable prognosis in patients with NPC.Further studies are needed to better understand the underlying mechanisms.