Objective To investigate the effects of prophylactic antiviral therapy for HBV DNA negative HBV-relat-ed hepatocellular carcinoma (HCC) patients undergoing hepatic arterial chemoembolization (TACE). Methods Fifty-four consecutive patients with HBV-related HCC and received TACE were enrolled in this study. Thirty patients received pre-emptive antiviral drugs before TACE were defined as the treatment group. Twenty-four patients, who did not use antiviral drugs until HBV reactivation after TACE, were included in control group. The incidence of HBV reactivation, duration from HBV DNA positive point to the last time of TACE, the occurrence of abnormal alanine aminotransferase (ALT) caused by HBV reactivation, the peak of aspartate aminotransferase (AST) and the number of liver failure caused by HBV reactivation were observed after TACE in two groups. Results The incidence of HBV reactivation, the occurrence of abnormal ALT, the occurrence of abnormal ALT caused by HBV reactivation, the peak ALT and peak AST were significantly lower in treatment group than those of control group (P ＜ 0.05). No liver failure caused by HBV reactivation was found in treatment group. There were four patients with liver failure caused by HBV reactivation in control group. There was no significant difference in cumulative survival rate between two groups (P=0.071). Conclusion It is suggested that preemptive antiviral therapy can prevent the reactivation of hepatitis B virus, prevent the deterioration of liver function,and decrease the occurrence of liv-er failure caused by HBV reactivation in patients receiving TACE.