Objective：To explore the effects and possible mechanisms of the arsenic trioxide（ATO）and small molecule tyrosine kinase inhibitor ponatinb on KG-1 cells in vitro. Methods：Effects of ATO and ponatinib on proliferation of KG-1 cells were detected by CCK -8，and the apoptosis was assessed by Annexin V - FITC. Reverse transcription quantitative polymerase chain reaction（q - PCR） analysis was used to detect the expression of apoptosis - related genes. Western blott was performed to explore the expression levels of apoptosis-related proteins，fibroblast growth factor receptor 1（FGFR1）and phosphorylated signal molecules. Results：①Both ATO and ponatinib effectively inhibited cell proliferation by dose dependent manners. The combination of the two drugs exhibited higher proliferation inhibition rate，less colony formation and more cell apoptosis compared to the single drug treatment. ②Compared with the DMSO group，treatment with either ATO or ponatinib led to significant down-regulation of Bcl-2，up-regulation of Bax and Caspase-3 （P ＜ 0.05）. The combination of the two drugs up-regulated the expression of Bax and Caspase-3 more than single drug treatment（both P ＜ 0.01）. ③Punatinib significantly inhibited the expression of FGFR1 gene and protein（both P ＜ 0.01），and the addition of ATO did not decrease FGFR1 expression further. Signaling pathway studies showed that ATO significantly inhibited the phosphorylation of MAPK，m - TOR，and STAT5，but had no significant effect on the phosphorylation of PI3K/AKT and STAT3. Ponatinib markedly inhibited the phosphorylation of STAT3/5，and FGFR1 expression（both P ＜ 0.001），but had no significant effect on the phosphorylation of PI3K/AKT and MAPK. The phosphorylation level of STAT3 was further down-regulated by the combination of the two drugs compared with ATO or pratinib monotherapy（both P ＜ 0.01）. Conclusion：ATO and ponatinib may inhibit KG - 1 cell proliferation and colony formation and induce cell apoptosis through different mechanisms. The combination of the two drugs can further enhance the inhibitory effect on KG-1 cells.