Objective To introduce the characteristics of tetrahedral framework nucleic acids (tFNA), focusing on its application in the treatment of osteoarthritis (OA) and relationship with microRNA (miRNA), and prospect the application of tFNA in the treatment of OA and the new idea of constructing miR-tFNA functional complex to treat OA. Methods Recent studies were extensively reviewed to analyze the mechanism of tFNA and its relationship with OA and miRNA. Results tFNA, a new type of new carrier, can not only play an indirect role in the treatment of OA as a small molecular carrier with therapeutic effect, but also play a direct role through the regulation of chondrocytes. It can bind with the miRNA that can regulate OA. The therapeutic effect of constructing tFNA functional complex loaded with miRNA has been verified in various diseases, and tFNA has advantages compared with other vectors. Conclusion tFNA, a novel framework nucleic acid structure, plays an important role in the treatment of OA. Constructing miR-tFNA functional complex may be an innovative idea in the treatment of OA.