Abstract: Gene therapy has made great progress in clinical transformation and application. However, the main challenge for gene therapy remains how to deliver nucleic acid drugs safely and effectively, especially to achieve on-demand delivery to target cells. Researchers have designed numerous redox-responsive nucleic acid delivery systems based on the abnormal redox environment at the lesion site. The redoxsensitive groups in the delivery systems undergo structural breaks or property changes after being oxidized or reduced, thereby enabling nucleic acid drugs to be released specifically at the lesion site and improving the efficacy. In this article, we reviewed the design ideas and principles of various redox-responsive nucleic acid delivery systems, as well as discussed their application and development prospects in the treatment of tumors and inflammation, aiming to provide references for the development and clinical transformation of nucleic acid drug delivery systems.