To explore the effect of homoharringtonine(HHT) combined with imatinib(IM) on proliferation and apoptosis of K562/G01 cells and its potential mechanism.K562/G01 cells were cultured with HHT and/or IM. CCK-8 assay was used to detect cell proliferation. Cell apoptosis and phosphorylated tyrosine levels were analyzed by flow cytometry. The expression levels of p210, PI3K, p-Akt and Akt protein were determined by Western blot.Compared with HHT or IM alone, drug combination significantly inhibited cell proliferation and induced apoptosis of K562/G01 cells (both P< 0.05). HHT combined with IM could inhibit the levels of phosphorylated tyrosine and phosphorylated Crkl and downregulate the expressions of p210, PI3K and p-Akt in K562/G01 cells.HHT combined with IM can synergistically inhibit proliferation and induce apoptosis of K562/G01 cells by suppressing the p210 expression and its kinase activity.