RNA interference (RNAi), a conserved evolutionary mechanism widely found in living nature, is considered for defending the alien gene and virus infection. RNAi can induce gene silencing by prohibiting the translation of the target mRNA, which is specially recognized by the corresponding siRNA, and finally degraded by the RISC. So RNAi can be applied as a new technology tool for the functional gene research and gene therapy. But the effects of random designed siRNAs on gene silencing differ greatly from each other. The design of the special, highly efficient siRNA comes to be a crucial problem. This issue gives an overview about the new progress of the siRNA design principle.