It has been proven that isoliquiritigenin could inhibit the proliferation of some kinds of cancer cell lines andhas a strong antioxidative activity. The purpose of this study is to investigate whether the antioxidantisoliquiritigenin affects the proliferation and redifferentiation in HL-60 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) colorimetric method and trypan blue staining were used to measure cellproliferentiation and survival. The morphological changes, nitroblue tetrazolium chloride (NBT) reductiveactivity, and the CD11b and CD14 surface antigens were used as the biomarkers of redifferentiation of HL-60cells. The intracellular reactive oxygen species (iROS) level was detected by a fluorescent probe, 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA). Isoliquiritigenin (ISL) inhibited the cell proliferation anddecreased the iROS levels in a dose-dependent manner, while the treatment did not increase the lethalityrate. After 72 h treatment with 10μg/ml ISL, a typical differentiated morphology was observed in HL-60 cells,including the decrease of karyoplasmic ratio and the increase of kidney-shape nuclear cells. The positive rate(%) of CD11b (26.4±3.90 vs 7.70±1.04, Pb0.01) and CD14 (20.4±2.30 vs 2.63±0.133, Pb0.01) cells increasedsignificantly. The NBT reductive activity increased 2.3-fold as compared to that of the control group. As anantioxidant, ISL decreased the iROS formation in a dose-dependent manner. All the results indicate that theantioxidant ISL is able to induce the monocytic differentiation in leukemia cells. ISL has the potential as adrug to cure leukemia with fewer side effects.