Background: Chronic hepatitis C (CHC) is a silent viral infection; however, elevated mortality and morbidity rates are noted in Egypt due to its adverse efects. The augmented incidence of diabetes in patients with viral C infection may be owing to glucose intolerance, high BMI, senility, and inherited factors. Objective: Little information is available about the connection between interleukin-28B (IL-28B) geno type in disease progression among CHC patients with diabetes. Thus, we aimed to assess the association between IL-28B genotype (rs12979860) in CHC with type 2 diabetes mellitus (T2DM) versus those without diabetes in disease progression among Egyptian patients. Results: CC genotype was signifcantly lower in diabetics than in non-diabetics (13.7% vs. 36.3%). While (CT/TT) were signifcantly higher in diabetics than in non-diabetics (CT 58.8% vs. 43.7%), (TT 27.5% vs. 20%) (p=0.03) and likewise alleles (p=0.04). Multivariate logistic regression analysis was signifcant with viral load p<0.001, alanine aminotrans- ferase (ALT) p<0.001, genotype CC versus TT p=0.04 & T2DM p=0.03. Conclusions: CC genotype might be used as a protective factor and TT genotype as a risk factor in disease progression among CHC patients with T2DM. Additionally, viral load, ALT & T2DM might interplay as predictors of disease severity. Detecting the genetic factors can be helpful in predicting and preventing the complications of diabetes associated with the hepatitis C virus (HCV).