Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus. About 70% of patients exposed to HCV develop a chronic infection, which can lead to scarring of the liver and ultimately to cirrhosis, liver failure, and hepatocellular carcinoma. For the past decade, the standard therapy for HCV infection has been a combination of interferon-α and ribavirin. In recent years, direct-acting antiviral agents, boceprevir and telaprevir, have been added to the therapeutic regimen and considerably improve the cure rates for HCV infection. However, the treatment continues to cause substantial side effects and is associated with drug resistance due to frequent mutations in the HCV RNA genome resulting from the low fidelity of its RNA polymerase. MicroRNAs (miRNAs) are a class of small, non-coding RNAs approximately 22 nucleotides in length. They are derived from cellular or viral transcripts and bind to their target mRNAs in a sequence-specific manner, resulting in either mRNA cleavage or translational repression and subsequent modulation of the expression of the majority of the protein-coding genes. miRNAs have been implicated in regulating multiple aspects of HCV life cycles and certain miRNAs serve as essential mediators for the interferon-based antiviral therapy. Furthermore, recent studies have documented the potential values of miRNAs as novel therapeutic targets against hepatitis C infectivity.