Cancer stem cells (CSC) are defined as cells with a tumor-initiating potential and are resistant to chemo-radiation therapy. Evasion of apoptosis is one of the hallmarks of human cancers attributed to CSCs. Human TRAIL/Apo-2L is a ligand of the TNF family that can trigger apoptotic cell death and has been demonstrated to induce apoptosis in a wide range of cancers. Interestingly, TRAIL receptor DR5 was found to be over-expressed in leukemic stem cells (LSCs). Inducing apoptosis in CSCs using TRAIL protein would be a novel and efficient strategy. We characterized and targeted the leukemic stem cells to induce self-death by TRAIL-based pathway. A fusion protein of IL2-TRAIL peptide was constructed to target leukemic cells over-expressing IL2 α receptor.