RNA interference (RNAi) has emerged as a powerful tool to suppress gene expression in a variety of cell lines by mediated small interfering RNAs (siRNA). In addition to the gene-silencing activity of siRNA, it can induce pro-inflammatory cytokines and type I interferon. RNA-sensing immonoreceptors include Toll-like receptor (TLR) family and cytosolic RNA-sensing proteins like Protein Kinase R (PKR), 2 َ -5 َ Oligo adenylate synthetase (2›-5›OAS), Retinoic-acid Inducible Gene –I (RIG-I), Melanoma Differentiation-associated gene-5 (MDA-5) and Nuclear Factor kappa B cell (NF-κB). Induction of IFN can be raised the signaling pathways associated with the TLR. Each of receptors group is able to induce signals in response to a variety of ligands, initiating the pro inflammatory cytokines response. This review article describes gene silencing, the role of cellular factors in innate immunity gene regulation and induction of interferon by double-stranded and single stranded siRNA.