Background: Hepatitis C virus (HCV) infection is a worldwide problem that is likely the cause of chronic hepatitis, liver cirrhosis, liver failure, and may underlie the development of hepatocellular carcinoma (HCC). Objectives: The ability of plasma level of MiR-126 gene expression determination to differentiate patients with HCV infection according to the probable response to treatment was evaluated. Patients and methods: Blood samples of 43 patients and 17 controls were obtained and processed for determination of serum aspartate transaminase (AST), alanine transaminase (ALT) and alpha-fetoprotein (AFP) in addition to plasma level of MiR-126 gene expression.The percentage of change in post-treatment sample was calculated. Results: Treatment significantly reduced serum AFP and plasma MiR-126 expression levels, while serum AST and ALT were non-significantly reduced. The percentage of change in post-treatment serum AFP and plasma MiR-126 were positively correlated. Receiver operating characteristic (ROC) curve analysis defined high pre-treatment serum ALT and low pre-treatment plasma MiR-126 levels as sensitive and specific predictors for response to treatment, respectively with moderate accuracy. Multivariate Regression analysis defined the low pre-treatment gene expression level of MiR-126 as the significant predictor for response to treatment. Conclusion: The gene expression of MiR-126 is correlated with the results of laboratory diagnostic tests for HCV infection, but has a significantly higher diagnostic value. Low gene expression of MiR-126 can discriminate samples of HCV responders to treatment.