Interferons (IFNs) can induce the expression of a series of interferon-stimulated genes (ISGs). As direct-acting antiviral factors, ISGs play important roles in host antiviral defense. More and more studies reveal that ISGs directly or indirectly target multiple steps of the virus life cycle. Since diverse ISGs have different structures and locations in the cell, they exert various antiviral actions through different pathways. This review aimed to give a brief introduction to ISGs expression induced by IFNs through the JAK-STAT pathway, and provide an overview of typical antiviral mechanisms of representative ISGs.