Objective： To explore the effects and possible mechanisms of the arsenic trioxide (ATO, AS2O3) and FGFR inhibitor ponatinb on KG-1 cells in vitro. Methods： Effects of ATO and ponatinib on cells proliferation were detected by [基金项目：常州市卫健委重大科技项目（编号ZD202213） *通讯作者（Corresponding author）,E-mail:848021532@qq.com.] CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of B cell lymphoma-2 (Bcl-2) , Bax，caspase-3 and FGR1. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2，Bax，Cleaved- caspase-3，FGR1 and the expression of p-PI3K/AKT/mTOR, p-MAPK, p-STAT3/5 and FGFR1. Results； ①ATO and ponatinib effectively inhibited cell proliferation by dose dependent manners. ATO combined with ponatinib synergistically inhibitted the viability of KG-1 cells, more significantly reduced the colony formation and induced apoptosis as compared to the single drug treatment. ②Treatment with either ATO or ponatinib at 1/2 IC50 led to significant increases in the expression levels of Bax, caspase-3, and decreases in the expression of Bcl-2(P<0.05). ATO combined with ponatinib synergistically increased Bax and caspase-3 mRNA expression as compared to the single drug treatment(P<0.001). The combination treatment also more significantly promoted the expression of Cleaved-Caspase-3 protein(P<0.001). ③Ponatinib markedly down-regulated the phosphorylation of STAT3/5, and FGFR1 expression(P<0.001), but not p-PI3K/AKT and p-MAPK. ATO significantly down-regulated p-MAPK, m-TOR, and p-STAT5, but not p-PI3K/AKT, p-STAT3and FGFR1. However, ATO enhanced the effect of ponatinib which decreased the phosphorylation of p-STAT3(P<0.01). Conclusion: ATO and ponatinib can inhibit KG-1 cell proliferation, colony formation and induce cell apotosis through different mechanism. The combination can further enhance the inhibitory on KG-1 cells.