Hypoxia induced microRNA-210 is implicated in ischemic disorders and in tumor progression. In the present study, we have used a knock out mouse model to investigate how miR-210 regulates angiogenesis. Our studies show that miR-210 sensitizes endothelial cells to bFGF-mediated signaling by targeting FGFRL1 which lacks a receptor kinase domain. FGFRL1 was found to be a negative regulator of bFGF induced pro-angiogenic signaling. In the absence of miR-210, FGFRL1 levels are increased in endothelial cells and as a consequence dampened hypoxia-induced vessel sprouting. miR-210 KO mice showed reduced angiogenesis of FGF-containing matrigel plugs. Furthermore, tumor angiogenesis was attenuated in miR-210 KO animals. These data suggest that miR-210 targets FGFRL1 and sensitizes endothelial cells to bFGF and regulates tumor angiogenesis.