Background and Aim: We analyzed whether insulin resistance (IR) assessed by homeostasis model assessment (HOMA2-IR) index can stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B virus (HBV) infection. Methods: A retrospective cohort of 1696 chronic HBV-infected patients (age: 50.07.8years, men=964 [56.8%]) who underwent detailed health checkup program including C-peptide and fasting blood glucose measurement and followed up for more than a year were analyzed. Results: During a median follow-up of 5.0years (range, 1.0-10.5years), 24 patients (1.4%) developed HCC. The HCC incidence rate was higher for patients with higher HOMA2-IR value than those with lower HOMA2-IR value (1.7% vs 0.5% for HOMA2-IR >1.200 vs <= 1.200, P=0.009). HOMA2-IR was a significant factor associated with HCC development in multivariable-adjusted model (HR [95% CI]: 3.25 [1.13-9.31], adjusted for age, sex, cirrhosis, and HBV DNA levels). The association between HOMA2-IR and HCC was markedly attenuated and became no longer statistically significant (HR [95% CI]: 1.93 [0.57-6.51]) when further adjusted for obesity, hypertension, and diabetes. In subgroup analysis, HOMA2-IR value was an independent factor associated with HCC in patients without overt metabolic abnormalities (hypertension, diabetes, and metabolic syndrome) but not for those with overt metabolic abnormalities. Conclusion: Insulin resistance assessed by HOMA2 was associated with the risk of HCC, indicating that HOMA2-IR can be a useful tool for stratifying the risk of HCC in chronic HBV-infected patients, particularly in patients without overt metabolic abnormalities.