Long non-coding RNAs (lncRNAs) are designated as the transcripts longer than 200 nucleotides without protein-coding capacity. As a category of important gene regulatory factors, lncRNAs regulate the expression of target genes at epigenetic, transcription and post-transcriptional levels by various mechanisms, such as chromatin remodeling, DNA modification, transcription inhibition and RNA-RNA interactions, etc. In recent years, studies have shown that many lncRNAs can be induced by viruses or interferon (IFN) and to regulate the expression of related antiviral genes in IFN-mediated antiviral innate immune responses. In this review, we focus on the regulation of lncRNAs in IFN-mediated antiviral innate immune responses, especially in the transcription of IFN-stimulated genes (ISGs). In addition, we summarize the regulatory network of lncRNAs, IFN and ISGs. This review will provide a valuable reference for the researchers working in this field.