RNA interference technology has been widely applied in biomedical therapy in recent years. A type of small RNA molecule - siRNA could regulate the expression of disease related genes by breaking down the integrity of mRNA with high specificity. However, the low efficiency of siRNA delivery to its target seriously hampered the RNAi therapy. Compared with viral-based delivery systems, non-viral-based nanoparticles are more suitable for disease treatment due to reduced cellular toxicity, higher loading capacity, and better biocompatibility. This review article highlights several nanoparticle-based siRNA delivery systems, including liposomes, cationic solid lipid nanoparticles, reconstituted high density lipoprotein, polymeric nanoparticles, cationic cell penetrating peptides, and inorganic nanoparticles. The molecular mechanism of gene silencing, clinical examples, and the limitations of current technology related to nanomaterial sciences, are also discussed.