RNA interference (RNAi) is a process of sequence specific post-transcriptional gene silencing induced by double-strand RNA (dsRNA) and this phenomenon was discovered in Caenorhabditis elegans (C. elegans) [10]. RNAi has been shown to function in higher organisms including mammals, and methods that exploit RNAi mechanisms have been developing. RNAi has now been well-established as a method for experimental analyses of gene function in vitro as well as in high-throughput screening, and recently, RNAi has been experimentally introduced into cancer therapy. To apply the RNAi phenomenon to therapeutics, it is important to select suitable targets for the inhibition of cancer progression and also to develop effective drug delivery systems (DDSs). Recently a lot of useful non-viral DDSs for small interfering RNAs (siRNAs) have been developed Besides selecting suitable targets, an important consideration for siRNA-mediated treatment is to predict and avoid off-target effects, which are the silencing of an unintended target gene, and potential immunostimulatory responses. To avoid those effects, the most specific and effective siRNA sequence must be validated. Modification of two nucleosides of the sense strand also completely co-inhibited the immunological activities of the antisense strand, while the silencing activity of the siRNA was maintained