Abstract: Objective To investigate the role of FBXO22 gene in the angiogenesis of breast cancer and its molecular biological mechanism. Methods FBXO22-si RNA was transfected into human breast cancer MDA-MB-231 and BT-549 cells, angiogenesis in vitro experiment observe the difference of vascular in two kinds of breast cancer cells after transfected; compared the effect of FBXO22-si RNA in two kinds of breast cancer on FBXO22, hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels by Western blot ; test the mRNA levels of HIF-1α and VEGF by Real Time-PCR after transfected into human breast cancer. Results Compared with group FBXO22-Ctrl, the number of vascular form in MDA-MB-231 and BT-549cells in the FBXO22-si group were increased 107.1% and 181.8% ; the expression of FBXO22 protein decreased 55.5% and 51.9% ; the expression of HIF-1 protein increased 39.3% and 68.4% ; the expression of VEGF protein increased 40.7% and 21.7% ; there were no significant changes in mRNA level of HIF-1α and VEGF. Conclusion FBXO22 plays an important role in angiogenesis as a tumor suppressor gene in breast cancer. After interfering with FBXO22, it can increase the expression of VEGF at the protein level and promote angiogenesis through the HIF-1α pathway.