Objective：To study the anti-angiogenic effect of arsenic trioxide(As2O3) on breast cancer，and explore the possible molecular mechanisms. Methods：Human umbilical vein endothelial cells(HUVECs) were cultured in tumor conditioned medium derived from MCF-7 and treated with 0，4，8 μmol/L As2O3. Cell wound healing assay，Matrigel assay，CCK-8 assay，and Annexin V assay were carried out to detect cell migration rate，angiogenesis ability，cell proliferation and cell apoptosis，respectively. Western blotting assay was used for detecting protein level. Results：Compared to the control group，the As2O3 treated groups showed reduced ability of cell migration and tube formation. A decline in cell proliferation and a rise in apoptosis were also found in the As2O3 groups. The protein expression of FoxO3a and its downstream genes Fas-L and p27Kip1 were increased following As2O3 treatment. Conclusion：As2O3 could attenuate the angiogenic ability of HUVECs by inducing cell apoptosis and inhibiting cell proliferation through upregulation of FoxO3a and activating of its downstream pathways，which suggested that As2O3 may play an important role in anti-angiogensis in breast cancer.