Nucleic acid drugs，as nucleotide drugs play a role on the gene level，have great potential in the treatment of some diseases such as cancer and viral infection. The therapeutic effects of traditional treatments are usually short⁃lived because they target proteins rather than underlying genes. Nucleic acid therapy，by contrast，can achieve long ⁃ term efficacy through gene suppression，addition，replacement or editing.At present，nucleic acid drugs mainly include DNA drugs，mRNA drugs and siRNA drugs. In this paper，we reviewed the working principle of these nucleic acid drugs，as well as the challenges and solutions of nucleic acid drugs in clinical application.