​Small interfering RNA (siRNA) has been identified as a useful therapeutic resource in cancer therapy. Molecular manipulation with siRNA has been reported to have high therapeutic potential on the cells with excessive gene overexpression or caused by mutation. However, siRNA therapeutic approaches are pursuing effective and efficient delivery systems for in vivo applications due to the lack of stable, low cell uptake, and the high likelihood of function loss due to enzymatic degradation. The chapter comprises various approaches used to improve siRNA delivery focusing on nanoparticles with a common goal and superior effectiveness. Besides, this chapter discusses problems and prospects for creating safe and effective siRNA delivery systems in cancer therapy, focusing on nanoparticles. Similarly, it assesses the recent progress achieved by nanomaterials, including biodegradables, liposomes, polyplex …​