Transdermal delivery of gene medicine holds a great promise in gene therapy, and electroporation-mediated method is a high-efficiency drug transfer technique. Traditional skin electroporation approaches require high voltage that may cause severe injure. In this chapter, we provide a detailed protocol of a novel skin electroporation approach via combination of a microneedle roller and a flexible interdigitated electroporation array (FIEA) for efficient delivery of DNA and siRNA into mouse skin. This electroporation protocol assisted by punching with the microneedle roller represents significant advantages over treatment with electroporation alone, allowing successful nucleic acid transportation at low voltage, with ideal safety outcomes. We describe the details of fabrication process of the FIEA, experiment preparation, and mouse thigh skin electroporation.