In this study, we selectively downregulated KGFR mRNA and protein expression in three epithelial cell lines, HaCaT keratinocytes, MCF-7 breast cancer cell and primary cultured keratinocytes (KCs), by a new approach of siRNA design, based on the utilization of DICER endonuclease substrate 27-mer dsRNAs to trigger RNA interference (RNAi). This evidence concerns the gene FGFR2 and breast cancer.