Gene silencing using RNAi (RNA interference), has recently been used as a successful laboratory technique in determining the function and control of gene expression and provides a wide range of applications in molecular biology and gene therapy. RNAi is a method of suppressing gene expression. In this direction, a single-stranded RNA molecule of about 21–23 nucleotides, called siRNA (small interfering RNA), is used. By influencing the target mRNA, these RNAs play an important role in regulating transcription, gene silencing and DNA demethylation. The transcribed mRNA for this purpose is broken down by the RNA-induced silencing complex (RISC). The use of these RNAs has prevented the proliferation and development of viral, bacterial, parasitic, and other infections. Although the use of the RNAi is considered as a powerful therapeutic approach, however, the delivery of siRNA to the cell has many limitations. The design of a variety of carriers, including nanoparticles, has revolutionized the siRNA delivery. These nanoparticles are designed to overcome one or more intracellular and extracellular barriers. The RNAi is evolving with extensive studies around the world. In this review article, using authoritative scientific sources, we examine the recent strategies for siRNA delivery and its challenges, and advances in the siRNA-mediated therapies are also considered.