Objective To explore the effect of FOXO 3 A on hematopoietic system damage induced by irradiationexposure in FOXO 3 A-knockout mice. Methods FOXO 3 A^{-/ -} and WT mice were divided into four groups: wild-type control(WT), FOXO 3 A^{-/ -} control ( FOXO 3 A^{-/ -} ), wild-type irradiation (WT+IR), and FOXO 3 A^{-/ -} irradiation ( FOXO 3 A^{-/ -} +IR). Mice received 4 Gy X-ray total body irradiation (TBI) at a dose rate of 0. 9 Gy/ min. Fourteen days later, peripheralblood measurements, bone marrow cell counts, organ index, bone marrow cell phenotyping, and CFU-GM of hematopoieticprogenitor cells were quantified. Results Under physiological conditions, bone marrow nucleated cell counts weredecreased and proportions of hematopoietic progenitor cells (HPCs) were increased in FOXO 3 A^{-/ -} mice ( P < 0. 05). Theseresults indicate an increased decline in the proportion of HPCs/ hematopoietic stem cells (HSCs), and reduced number ofbone-marrow nucleated cells and colony forming unit-granulocyte and macrophage (CFU-GM) ( P < 0. 001) in FOXO 3 A^{-/ -}mice 14 days after 4 Gy X-ray TBI. Conclusions FOXO 3 A gene knockout damaged the homeostatic maintenance of thehematopoietic system, and aggravated HPC and HSC injury in TBI mice. The role of FOXO 3 A in regulation of hematopoietic system damage induced by radiation exposure and clinical translation remain to be further studied