Hepatitis C virus (HCV) infection has become a serious global public health problem. Interferon (IFN) therapy is the traditional anti-HCV method, playing antiviral role through Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway. Suppressor of cytokine signaling 3 (SOCS3) is one of the important negative regulatory factors in this pathway. The expression level of SOCS3 is closely related with host IFN resistance. HCV infection and IFN therapy can change the expression level of host microRNA, and microRNA targeting SOCS3 can participate in host anti-HCV replication by regulating SOCS3 expression level.