Electroporation-mediated gene transfer (electro-transfection) is a powerful tool to introduce nucleic acid compounds such as plasmid DNAs, antisense oligonucleotides, and short interfering RNAs (siRNAs) into the cells. Electro-transfection is a physical gene transfer method that utilizes an electrostatic field generated with an electroporator apparatus. Here, we demonstrate a practical protocol for electro-transfection (electro-delivery) of siRNA into cells in vivo and further demonstrate the application of the method to cancer therapy. We successfully developed an original electrode (the plate and fork-type electrode) and used it for in vivo electro-delivery of siRNA. Vascular endothelial growth factor (VEGF), an angiogenic factor, was chosen as a model target gene. Electro-delivery of an siRNA targeting VEGF into the xenografted tumors in nude mice significantly suppressed the growth of tumors. By repeating the therapy with a chemically modified siRNA after an interval of 20 days, satisfactory anticancer effects were achieved.