Abstract: The treatment of chronic diseases is currently hampered by complex etiology, prolonged disease progression, and poor medication compliance and persistence. However, these challenges have also spurred the improvement, iteration, and innovation of treatment strategies for chronic diseases. Small interfering RNA drugs precisely target and silence pathogenic genes with the advantages of reduced drug resistance and prolonged therapeutic efficacy, thus being able to significantly reduce the frequency of dosing and improve compliance in patients with chronic diseases. siRNA drugs, which are being increasingly labelled as "innovative treatments for chronic diseases" and accelerating the formation of a "new quality productivity" of innovative drugs, are expected to overturn the current chronic disease treatment model. This review provides an overview of the mechanism of action, chemical modifications, delivery systems, and pharmacokinetic profiles of six siRNA drugs approved for commercial use between 2018 and 2023. It focuses on chronic diseases such as hypertension, hyperlipidemia, non-alcoholic steatohepatitis, chronic hepatitis B, and Alzheimer's disease, and provides an overall review of recent advances in siRNA drug research in the field of chronic diseases, from preclinical to clinical stages of development, with the aim of providing some insight for the development of siRNA-based nucleic acid drugs in the field of chronic diseases.