Neutrophil apoptosis is delayed in medical conditions associated to anoxia or hypoxia, prolonging tissue destruction and fostering the inflammation. Hypoxia Inducible Factor-1α (HIF-1α), is a main regulator of delayed neutrophil apoptosis but the mechanism of action is poorly characterized. Neutrophil gelatinase-associated lipocalin (24p3) participates actively in iron metabolism and the regulation of iron-responsive genes. Recently, a connection has been described between HIF-1α and 24p3. The purpose of the present study was to determine whether constitutive apoptosis in neutrophils requires 24p3 and whether HIF-1α represses 24p3 affecting cell death iron intracellular levels. To this end we used in vivo ischemic models and anoxic approaches based on the reactivation of the delayed apoptosis. We found that the stabilization of HIF-α during anoxic periods provoked a delay in neutrophil apoptosis through decrease of 24p3 expression and intracellular iron content. The ischemia drastically inhibited the synthesis of 24p3 in circulating neutrophils, increasing the tissue damage. Reactivation of neutrophil apoptosis with opsonized E.coli induced increases in intracellular levels of iron and 24p3. In conclusion, contrary to other cell types, constitutive apoptosis in neutrophils requires 24p3. During hypoxia or ischemia, HIF-1α stabilization represses 24p3 expression, consequently iron levels are depleted and neutrophil apoptosis is delayed.