Abnormal mechanical loading is the main risk factor for the development of osteoarthritis (OA), and it can lead to collagen degradation, glycosaminoglycan loss and chondrocyte apoptosis, as well as damage to articular cartilage and subchondral bone. However, due to the lack of understanding in chondrocytes mechanotransduction pathway and invalid method of cartilage repair and regeneration, there is an urgent need for understanding chondrocytes mechanotransduction pathway and mechanism of cartilage damage induced by mechanical loading. In this review, how chondrocytes sense and transmit mechanical signals from cell membrane to cecullar mechanosensors is introduced in detail, and the role of chondrocytes mechanotransduction in OA development is discussed with emphasis.