AIM To determine the role of diabetes mellitus (DM) and other associated factors in Chinese hepatocellular carcinoma (HCC) patients with cirrhosis, compared with those HCC patients without cirrhosis, in the single setting of hepatitis B virus (HBV) infection, after other known concomitant diseases were excluded METHODS A total of 482 patients, treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period January 2003 to June 2009, and with a hospital discharge diagnosis of HCC, were included Demographic, clinical, laboratory, metabolic and instrumental features were analyzed RESULTS Of the total, 310 patients were diagnosed with HBV infection and, following the inclusion and exclusion criteria, 224 were analyzed, including 122 patients (54 5%) with cirrhosis (the case group) and 102 patients without cirrhosis (the control group) Twenty-seven patients (12 1%) were diabetic, including 19 in the case group and 8 in the control group (19/122 = 15 6% vs 8/102 = 7 8%, P = 0 077) Thirty-one possible relevant parameters were compared by univariate analysis, and 9 variables were selected for multivariable analysis, including DM (P = 0 077), past history of HBV infection (P = 0 005), total bilirubin (P < 0 001), albumin level (P < 0 001), international normalized ratio (INR) (P < 0 001), alanine aminotransferase (P = 0 050), platelet (P < 0 001), total cholesterol (P = 0 047), and LDL cholesterol (P = 0 002) levels Diabetes showed a statistical difference by multivariable analysis [odds ratio (OR) 4 88, 95% confidence interval (CI) 1 08-21 99, P = 0 039], although no significant difference was found in univariate analysis In addition, three cirrhosis-related parameters remained statistically different, including INR (OR 117 14, 95% CI 4 19-3272 28, P = 0 005), albumin (OR 0 89, 95% CI 0 80-0 99, P = 0 027), and platelet count (OR 0 992, 95% CI 0 987-0 999, P = 0 002) CONCLUSION Besides the three cirrhosis-related parameters, DM was found to be the sole independent factor associated with HCC in patients with HBV-related cirrhosis, compared with those without cirrhosis (C) 2010 Baishideng All rights reserved