It is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha (HIF1α)/vascular endothelial growth factorA (VEGFA) axis to promote angiogenesis in breast cancer. However, it is unclear how this axis is negatively regulated. Inthis study, we demonstrated that miR-153 directly inhibits expression of HIF1α by binding to the 3′UTR of HIF1A mRNA,as well as suppresses tube formation of primary human umbilical vein endothelial cells (HUVECs) and breast cancerangiogenesis by decreasing the secretion of VEGFA. Importantly, expression of miR-153 was induced by hypoxia-stimulated ER stress, which activates IRE1α and its downstream transcription factor X-box binding protein 1 (XBP1). X-boxbinding protein 1 directly binds to the promoter of the miR-153 host gene PTPRN and activates transcription. These resultsindicate that hypoxia induces miR-153 to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis and miR-153 couldbe used for breast cancer anti-angiogenesis therapy.