Osteoarthritis (OA) is a common joint degenerative disease. Its pathological changes involve articular cartilage, subchondral bone, ligaments, joint capsule and synovium. Its main manifestations are progressive cartilage degeneration and secondary hyperostosis. Early treatment options for OA include exercise and medication, but when the condition worsens, surgical treatment is required. With the continuous disclosure of human genome information, gene therapy provides a new way to solve OA. Gene therapy utilizes viral or non-viral vectors to transfer target genes into the degenerative joint cavity, enabling stable, controllable and targeted expression of target genes in joints. By reducing local inflammation, inhibiting cartilage matrix degradation and promoting cartilage matrix synthesis, gene therapy protects and repairs damaged cartilage. This article reviews the effects of OA gene therapy on inflammation and cartilage matrix metabolism, gene delivery systems, micro ribonucleic acid (microRNA) and Long non-coding ribonucleic acid (LncRNA).