The present invention relates to a pharmaceutical composition for preventing or treating arthritis, including, as an active ingredient, a material which inhibits the expression of the hypoxia-inducible factor-2α (HIF-2α) gene or the activity of the HIF-2α protein. According to the present invention, the HIF-2α of the present invention increases the expression thereof in chondrocytes or tissue in which osteoarthritis is induced, and triggers the expression of various cartilage degeneration factors and the activation of mitogen-activated protein (MAP) kinase. In addition, when HIF-2α is inhibited, the expression level of cartilage degeneration factors and the phosphorylation of MAP kinase are significantly reduced by the inhibited degree of HIF-2α. Thus, the composition of the present invention may be applied to the prevention or treatment of arthritis, and may be used for the development of therapeutics for arthritis.