Interaction with microenvironmental factors is crucial for the regulation of hematopoietic stem cell (HSC) function. Stroma derived factor (SDF)-1 alpha supports HSCs in the quiescent state and is central to the homing of transplanted HSCs. Here, we show that integrin signaling regulates Sdf-1 alpha expression transcription-ally. Systemic deletion of Periostin, an Integrin-alpha v ligand, showed increased expression of Sdf-1 alpha in bone marrow (BM) niche. Pharmacological inhibition or CRISPR-Cas9-mediated deletion of SRC, resulted in a similar increase in the chemokine expression in vitro. Importantly, systemic SRC-inhibition led to increase in SDF-1 alpha levels in BM plasma. This resulted in a robust increase (14.05 +/- 1.22% to 29.11 +/- 0.69%) in the homing efficiency of transplanted HSCs. In addition, we observed enhancement in the recovery of blood cell counts following radiation injury, indicating an enhanced hematopoietic function. These results establish a role of SRC-mediated integrin signaling in the transcriptional regulation of Sdf-1 alpha. This mechanism could be harnessed further to improve the hematopoietic function.