MicroRNAs (miRNAs) are a class of small, evolutionarily conserved, noncoding RNA that regulate several important cellular processes. The versatility of these molecules allowed the accurate predictions that they would also affect the replication and life cycle of HCV. In this review, emphasis has been given to two selected miRNAs: miR-155 and miR-196b. Recent data indicate that miR-155 is overexpressed in HCV-infected patients, inducing an inflammatory state, and promoting virus replication and persistence even after the completion of antiviral treatment. It is also associated with the increased proliferation and inhibited apoptosis of hepatocytes, which promotes the growth of liver tumors. In contrast, miR-196b is reported as a factor inhibiting HCV replication with cytoprotective, anti-inflammatory, and antioxidant properties. Growing evidence suggests that these molecules could be used as potential prognostic and predictive factors and their antagonists or mimics as a promising therapeutic approach in HCV-infected patients. Copyright © 2014 John Wiley & Sons, Ltd.