Abstract：Objective：To investigate the role of artesunate(ART) in inhibiting the growth of chronic myeloid leukemia(CML) cells and inducing its apoptosis based on endoplasmic reticulum stress related inositol requiring enzyme 1α(IRE1α)/ cAMP- response element binding protein(CREB)/ NOD- like receptor 1(NLRP1) pathway. Methods： After intervening K562 cells by ART with the concentration of 0 μg /mL，12.5 μg /mL，25.0 μg /mL，and 50.0 μg /mL respectively，the cell survival and proliferative activity， the cycle distribution after cell apoptosis， the changes in the contents of glutathione(GSH) and reactive oxygen species(ROS)，and the expressions of IRE1α/CREB/NLRP1 were observed. Results：Compared with those in the control group respectively，ART with the concentration of 12.5~50 μg/mL could significantly inhibit the proliferation and growth of K562 cells and induce the apoptosis(P＜0.01)；the levels of total GSH and GSH，activity of glutathione reductase (GSH- Rd) and glutathione peroxidase(GSH- Px) in K562 cells was decreased(P＜0.05)； ROS content was increased(P＜ 0.05)； expressions of IRE1α， p- CREB mRNA and protein were decreased(P＜0.05)； expressions of CREB mRNA and protein were increased in the group of 25.0 μg /mL ART and 50.0 μg /mL ART(P＜0.05)；but there was no significant effect on expressions of NLRP1 mRNA and protein. Compared with 12.5 μg/mL ART，50.0 μg/mL ART can reduce the levels of total GSH and GSH，activity of GSH-Rd and GSH-Px as well as expressions of IRE1α，p-CREB mRNA and protein in K562 cells (P＜0.05)；the expressions of CREB mRNA and protein were increased in the group of 25.0 μg /mL ART and 50.0 μg /mL ART (P＜0.05). Conclusion： ART can significantly inhibit the activity and proliferation of K562 cells， induce their apoptosis， significantly reduce the GSH contents in the cells and increase the ROS contents， which may be realized by IRE1α/CREB/ NLRP1 pathway.