<p>A large number of ribonucleotides are present in the nucleus, and this specialized environment can be effectively targeted to enhance the efficiency of gene transfection. In this work, a gene transfection platform based on ribonucleotide-responsive silicon nanowire arrays (SN) was developed in order to improve the gene transfection efficiency. Briefly, low molecular weight polyethyleneimines (PEI) respectively modified by phenylboronic acid (PBA) and <span>d</span>-glucuronic acid (Glc) can be cross-linked by boronic ester bond. This cross-linked high molecular weight PEI can be bound to SN modified with PBA and loaded with DNA via electronic interactions. When the nanowire on the SN pierces the nucleus, the boronic ester bond responds to a large number of ribonucleotides and breaks. The dispersed PEI causes a decrease in charge density thus leading to a successful release of DNA. In addition, cleaved small molecular weight PEI can greatly reduce cytotoxicity. Over 90% of DNA can release from the material surface after ribonucleotide treatment. Compared with SN, the survival cell number is increased from 1800 to 62,000&#xa0;cm⁻², and the up to 98% cells are transfected. In conclusion, our results suggest that ribonucleotide-responsive SN is a novel, efficient, and safe platform for gene transfection.</p> Graphical abstract <p></p>