Abstract: Osteosarcoma (OS) is the most common bone cancer with high degree of malignancy. The worldwide disease incidence is 4/105 per year. OS is prone to young people who grow faster. Males have a higher incidence than females. But OS pathogenesis has not been clear to date. Now, we are going to make a brief review on the risk factors, such as amplifi cation of homologous chromosomes 6p21, 8q24 and 12q14, 10q21.1 heterozygote lost, abnormal expressions of tumor suppressor genes p53 and Rb, disorders of transcription factor activator protein -1 (AP -1), protooncogene, transforming growth factor (TGF), insulinlike growth factor (IGF) and connective tissue growth factor (CTGF), interaction of WWOX, miRNAs, and 14q32 miRNAs-cMYC, silence of miRNA-29a, etc.. These factors will open a novel avenue in the prevention and treatment of osteosarcoma.