Here, we reported that low-dose chidamide could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine), as well as induce apoptosis and cell cycle arrest in leukemia stem-like cells and primary refractory or relapsed CD34+ AML cells, particularly for those carrying high peripheral blood WBC counts (>30 × 109/l) at diagnosis, in association with DNA damage reinforcement or impaired DNA damage repair, and finally initiate caspase-3 and poly-(ADP-ribose) polymerase (PARP) cleavage. The gene discussed is CD34; the disease is leukemia.