Transient receptor potential vanilloid 1 is a non-selective cation channel, which is sensitive to heat, acidic environment and capsaicin. It is widely expressed in sensory neurons and various other tissues, and is closely associated with the development of several orthopedic disorders. Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by articular cartilage degeneration, synovial inflammation and subchondral bone remodeling. In recent years, with the deepening of research, it has been found that Transient receptor potential vanilloid receptor 1 (TRPV1) plays an important role in the pathophysiological process of KOA, affecting the progression of the disease by regulating pain transmission, inflammatory response, ferroptosis of chondrocytes, bone homeostasis and other mechanisms. In recent years, by targeting the TRPV1 channel to maintain the homeostasis of the joint environment, certain breakthroughs have been made in the relief of symptoms and the prevention and treatment of KOA, showing a good application prospect. This review outlines the mechanisms and regulatory pathways of TRPV1 and discusses its roles in chondrocytes, synovial tissue, and subchondral bone, as well as its pathological relevance in the development of KOA. It further summarizes current strategies for targeting TRPV1 in KOA therapy and the progress of related therapeutic interventions. The aim of this study is to expand the treatment of knee osteoarthritis and provide new treatment ideas and strategies for KOA patients.