Hepatitis B virus (HBV) infection is one of the main etiologies of hepatocellular carcinoma (HCC). We explored the impact of HBV DNA levels on the prognosis of patients with advanced HCC. The study was based on patients with advanced HCC and chronic HBV infection enrolled into three phase II trials evaluating first-line antiangiogenic therapy. Pre-treatment HBV DNA levels were measured by real-time quantitative polymerase chain reaction. Seventy-two patients were included. Patients with detectable HBV DNA levels had poorer median overall survival (OS) compared to patients without detectable levels (4.8 vs. 9.3 months, p=0.037). After adjusting for other clinicopathologic variables, the baseline HBV DNA level was an independent predictor of poor OS (p=0.014). Baseline HBV DNA levels were not correlated with progression-free survival or disease control rate. Baseline HBV DNA levels were associated with the prognosis of patients with chronic HBV infection receiving antiangiogenic therapy for advanced HCC.