OBJECTIVE： To investigate the preventive effect of entecavir against HBV reactivation of nasopharyngeal carcinoma therapy. METHODS： 87 inpatients with HBV-DNA positive nasopharyngeal carcinoma were selected from the Affiliated Hospital of Guilin Medical College during May 2010-Jul. 2012 as research group， and 79 inpatients with HBV-DNA positive nasopharyngeal carcinoma were selected from the hospital during May 2005-Jan. 2007 as control group. Control group was treated by routine radiotherapy and chemotherapy. Research group was given Entecavir dispersible tablet one week before radiotherapy or chemotherapy， 0.5 mg each day， and completed treatment course according to disease condition. Clinical outcome， the levels of serum HBV-DNA and ALT and liver function Child-Pugh grades before and after treatment were observed and compared between 2 groups. RESULTS： 3.45％ of patients suspended treatment in research group due to HBV reactivation and 11.39％ in control group， with statistical significance（P＜0.05）. After 4 weeks of treatment， HBV-DNA PCR and ALT level of research group decreased significantly compared to before treatment and control group， with statistical significance （P＜0.05）. There were no statistical significance in liver function Child-Pugh grades between 2 groups before and after treatment （P＞0.05）. CONCLUSIONS： Prophylactic application of entecavir can significantly reduce the rate of HBV reactivation in nasopharyngeal carcinoma therapy.