Reactive oxygen species (ROS) are bioactive oxygen molecules produced after exposure to exogenous oxidants or endogenously through cellular aerobic metabolism. Hematopoietic stem cells (HSC) are multipotent, self-renewing stem cells residing in hematopoietic tissues. Recent studies show that an abnormal increase in ROS production is associated closely with HSC senescence. Many signaling molecules such as FoxOs, ATM, mTOR, TSC1, Bmi1 and AKT play a significant role in ROS-induced HSC senescence. The roles of p53-p21 and p16-Rb pathways can induce hematopoietic dysfunction and lead to ROS-induced HSC senescence. This review summarizes the recent progress of studies on ROS-induced HSC senescence, and further elaborates the potential signaling molecules and pathways, aiming to provide a new target and thread for clinical treatment.