Osteoarthritis (OA) is a common degenerative disease that affects the vast majority of the elderly and may eventually embark on the road of the total knee arthroplasty (TKA), although controversy still exists in the medical community about the best therapies for osteoarthritis. Compared with physical therapy, oral analgesics and other non-operative treatments, intra-articular injection is more safe and effective. Moreover, intra-articular injection is much less invasive and has fewer adverse reactions than surgical treatment. This article reviews mechanism, benefits and adverse reactions of corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), mesenchymal stem cell (MSCs), stromal vascular fraction (SVF) and other new therapies (for example: gene therapy). The application prospect of intra-articular injection was analyzed according to the recent progress in drug research.