The human ether-a-go-go-related (herg) gene encoding K+ channels (HERG) belongs to an evolutionarily conserved multigene family of voltage activated K+ channels. The functional properties of HERG K+ channels are complex and their contribution to the repolarization of the cardiac action potential are well understood. Recent studies revealed that HERG K+ channels are preferentially expressed in different histogenesis of tumor cells. Leukemia is a cancer that originates in the bone marrow hematopoietic stem cells (HSCs). Leukemia stem cells (LSCs) are critical in the perpetuation of the disease. A better understanding of LSCs and molecular biology will allow the design of more effective therapies. We report in this study that herg was expressed in CD34+/CD38−/CD123high LSCs but not expressed in normal bone marrow CD34+/CD38− HSCs. In addtion, herg is also expressed in leukemia cell lines K562 and HL-60 and almost all the primary leukemia cells whereas not in the normal bone marrow cells. In addition, the expression of herg mRNA was not associated with the clinical and cytogenetic feature of leukemia. Moreover, HERG K+ channels can regulate leukemia cells proliferation and cell cycle. These data provide evidence for the oncogenic potential of HERG K+ channels and it may be a novel, potential pharmacological target for leukemia therapy in the future.