IFN-beta is induced via a c-fos dependent mechanism that is present downstream of the receptor activator of NF-kappaB ligand (RANKL)-RANK signal transduction cascade during osteoclast differentiation. Increased production of IFN-beta in turn inhibits osteoclastogenesis. However, the mechanism by which IFN-beta exerts its suppressive function remains unclear. In the present study, we found that miR-155, an IFN-beta-induced miRNA, mediated the suppressive effect of IFN-beta on osteoclast differentiation by targeting SOCS1 and MITF, two essential regulators of osteoclastogenesis. These findings have not only demonstrated that miR-155 inhibits osteoclast differentiation, but also provided a new therapeutic target for treatment of osteoclast-mediated diseases.