As₂O₃ is a Chinese traditional medicine. In previous study, 1.0 μmol/L As₂O₃ have been found that could induce MG-63 cell apoptosis in vitro. And then it was identified that IEX-1 gene expression was down regulated after the addition of 1.0 μmol/L As₂O₃ using cDNA Array, RT-PCR, Northern blot. IEX-1, a recently discovered early response gene, regulates cell growth and apoptosis. The exact transcriptional mechanism of IEX-1 was found using Dual-luciferase assay, EMSA, Western blot. Transcriptional factor p53 was up-regulated after the addition of 1.0 μmol/L As₂O₃, and the increased p53 protein bind the promoter region of IEX-1 gene, which repress the transcription and result in down-regulation of IEX-1 gene expression. It is further confirmed that IEX-1 gene is associated with osteosarcoma and the exact transcriptional mechanism of IEX-1 after the addition of As₂O₃ was found.