The role of IL-2 in HSC maintenance is unknown. Here we show that Il2(-/-) mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho-and erythropoiesis, myelopoiesis was enhanced in Il2(-/-) mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2(-/-) mice shows that the IL-2-Treg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of Treg activity resulted in increased IFN-gamma production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg population successfully rescued HSC maintenance in Il2(-/-) mice, preventing IFN-gamma activity could do the same even in the absence of Treg cells. Our study suggests that equilibrium in IL-2 and IFN-gamma activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-gamma treatment might help to restore hematopoiesis.