Osteoarthritis (OA) has become one of the most important diseases that endanger the physical and mental health of the elder all around the world. Hypertrophic changes of chondrocytes could occur in OA frequently. Hypertrophic chondrocytes express some typical biological markers, which mediate the progression of OA. Chondrocyte hypertrophy is regulated by multiple molecular signaling pathways, including Wnt, TGF-β, IHH/PTHrP and et al. In addition, the process of chondrocyte hypertrophy is gradually developed in different stages of OA, and to some extent, the progress of chondrocyte hypertrophy aggravated the severity of OA. In summary, elucidating the role in the pathogenesis of chondrocyte hypertrophy will help to understand the pathogenesis of OA, and further guide the clinical treatment of OA.