Hemoglobin glycation index (HGI) is the difference between the measured HbA1 level and the predicted HbA1c value on the basis of plasma glucose concentrations. HGI represents a measure of hemoglobin non-enzymatic glycation degree, found to be positively associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Since an increased non-enzymatic protein glycation may contribute to hepatic damage, in this study we investigated the relationship between HGI and hepatic fibrosis risk in a cohort of 517 non-diabetic individuals. Subjects were stratified into quartiles according to HGI levels. The severity of hepatic fibrosis risk was estimated by the validated Fibrosis-4 (FIB-4) score (FIB-4<1.3 low risk, ≥1.3 to <2.67 intermediate-risk, ≥2.67 high risk). As compared to individuals in the low HGI group (quartile 1), those in the intermediate (quartile 2 and 3) and high (quartile 4) HGI groups have increased BMI. After adjusting for BMI, subjects in the intermediate and high HGI groups exhibited progressively increased levels of total cholesterol, triglycerides, and higher concentrations of the liver damage biomarkers aspartate aminotransferase and C reactive protein as compared to the lowest quartile of HGI. Notably, subjects in the high HGI group had significantly augmented values of FIB-4 score in comparison to the lowest quartile (0.99+0.74 vs 0.85+0.25, p=0.01). Proportion of subjects having intermediate or high risk of advanced hepatic fibrosis was progressively increased in the intermediate (11% and 0.8%, respectively) and high HGI (17.2% and 0.8%, respectively) groups as compared to the lowest quartile of HGI (5.5% and 0%, p=0.002). In a logistic regression analysis adjusted for potential confounders, subjects with higher HGI levels have a 4-fold increased risk of having intermediate/advanced fibrosis as compared to those in the lowest HGI quartile (95%CI 1.38-10.96, p=0.01). In conclusion, our results demonstrate that high HGI levels are associated with an increased risk of hepatic fibrosis in non-diabetic subjects independently of other metabolic risk factors.