Osteoarthritis is the most common articular disease that has significantly affected the patients’ quality of life. As cartilage doesn’t have any blood vessels and neurons, its treatment is a difficult task to do. Traditional therapeutic approaches, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and surgical interventions, can only control the disease, and the joint will lose its functionality after a short period. Consequently, modern methods such as cell therapy and tissue engineering along with using various biomaterials are being attempted to repair degenerated cartilage tissue. Using interfering RNAs is another approach that targets specific destructive or malfunctioned RNA sequences and suppresses the responsible factors for cartilage tissue destruction. Hence, the degenerated tissue can gradually retain the balance between anabolic and catabolic activities. Identification of the affecting genes in degeneration or malfunctioning and their suppression has provided promising results for the treatment of diseases. In the current study, after introducing the tissue, the process of cartilage degeneration and osteoarthritis development, the researches that have investigated the effect of interfering RNAs on rehabilitating cartilage tissue via inhibition of cartilage matrix destruction are reviewed.