Kashin-Beck disease (KBD) is an endemic, disabling and deforming osteoarthropathy and mainly affects children or teenagers in growth and development period (Yamamuro 2001). The mainly pathological changes in KBD are degeneration and necrosis in joint cartilage and epiphyseal plate cartilage (Guo et al. 2014). The disease has been found for over 160 years, but its etiology remains unclear. The epidemiological investigation of environmental risks has shown that selenium (Se) deficiency may contribute to the etiopathogenesis of KBD, and Se supplementation could significantly decrease the incidence of KBD (Mo et al. 1997). Thus, it is considered that Se deficiency is a main environmental factor of KBD, however, the exact molecular mechanism for KBD treatment with Se is still obscure. Screening of KBD susceptibility genes and related functional experiments were conducted to examine the relationship between the molecular mechanism of Se and selenoprotein on chondrocyte oxidative stress, inflammation and apoptosis-signaling pathways. These efforts will further search for new molecular targets for the early diagnosis, warning, prevention, and treatment of KBD.