Necrosis of the femoral head (NFH) is an orthopedic disease characterized by a severe lack of blood supply to the femoral head and a marked increase in intraosseous pressure. NFH is associated with numerous factors, such as alcohol consumption and hormone levels. The present study focused on the expression levels of osteoprotegerin (OPG) in NFH and the effect of overexpression on chondrocyte apoptosis. The results demonstrated that expression was markedly decreased in the femoral head of patients with NFH compared with normal femoral heads. Lentivirus-mediated overexpression of in human chondrocytes reversed the decrease in cell viability and the increase in reactive oxygen species production induced by an oxidative stress-inducing factor, -butyl hydroperoxide. Flow cytometry and TUNEL assays revealed that overexpression inhibited the apoptosis of chondrocytes. In addition, it was revealed that exerted its anti-apoptotic effect mainly by promoting Bcl-2 expression and Akt phosphorylation and inhibiting caspase-3 cleavage and Bax expression. The present study revealed that may be an important regulator of NFH.