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Backgrounds: Chronic hepatitis C virus (HCV) infection has been associated with induction of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMC). We aimed to evaluate the role of PBMC-miRNAs in the treatment outcome to antiviral therapy for HCV genotype 1 (HCV-1) patients., Methods: Treatment-naive chronic HCV-1 patients, including 13 in screening phase and 48 in validation phase, were treated with 48weeks of peginterferon/ribavirin. The primary end-point was the achievement of a sustained virological response (SVR, HCV RNA undetectable during 24weeks post-treatment follow-up). Expression profiling of PBMC-miRNAs was performed by quantitative PCR-based array in typical responders and null-responders. Then candidate PBMC-miRNAs were validated by quantitative PCR in an independent validation set., Results: PBMC-miR-125b was significantly predictive of an SVR, with expression levels of 5.28-fold lower in sustained responders versus null-responders (p=0.0163). In multivariate analysis, PBMC-miR-125b was significantly associated with the achievement of SVR (per 2-fold decrease, odds ratio/95% confidence interval (OR/CI): 2.07/1.14-6.31) independent of sex, age and interleukin-28B genotype. In patients who did not achieve a rapid virological response (RVR, undetectable HCV RNA at treatment week 4), PBMC-miR-125b was the only predictive factor of an SVR (per 2-fold decrease, OR/CI: 2.07/1.14-6.31). However, the circulating and hepatic miR-125b did not show significant difference between responders and non-responders., Conclusions: PBMC-miR-125b expression levels were inversely related to the achievement of an SVR in HCV-1 patients, independent of interleukin-28B genotype, and was the single predictor of SVR in non-RVR patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)