BACKGROUND This study aimed to investigate whether diabetes mellitus (DM) increased the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. MATERIAL AND METHODS Individuals with a confirmed diagnosis of HCC and chronic HBV infection (n=112), and non-diabetic individuals with both chronic HBV infection and HCC (n=210), were matched by age, sex, and degree of liver cirrhosis. Demographic, lifestyle, and clinical data were reviewed. Data were analyzed by univariate and multiple logistic regression analysis to identify the risk factors for HCC. RESULTS Of the 112 patients with HCC (median age, 52.0 years; range, 46.3-56.0 years), 18.8% were men, and the prevalence of cirrhosis was 90.2%. Of the 210 patients without HCC (median age, 51.0 years; range, 47.0-58.0 years), 26.2% were men, and the prevalence of cirrhosis was 91.9%. Diabetes mellitus was more prevalent among individuals with HCC (16.1%) compared with those without HCC (7.6%) and increased the risk for HCC by two-fold to three-fold (adjusted odds ratio [AOR]: 2.402; 95% confidence interval [CI], 1.150-5.018). Multivariate analysis showed that cigarette smoking significantly increased the risk of HBV-related HCC (AOR: 1.665; 95% CI, 1.031-2.690), as did increased levels of HBV DNA (≥10³ IU/mL) (AOR: 1.753; 95% CI, 1.079-2.849). CONCLUSIONS In a Chinese population with chronic HBV infection, DM increased the risk of HCC, as did cigarette smoking and high levels of HBV DNA. Screening patients with known risk factors for HCC might improve early detection rates and treatment to prevent tumor progression.