In addition to the clinical applications as antimalarial agents, artemisinin and its derivatives have demonstrated significant potential in antitumor drug discovery. To enhance antitumor activity, a novel series of artemisinin-containing histone deacetylase (HDAC) inhibitors was designed using a hybrid strategy that fused the artemisinin moiety with HDAC inhibitory functionality. A triazole ring was incorporated into the linker region to improve water solubility. Among these derivatives, compound Hj-9 exhibited broad spectrum and especially potent antitumor activity against acute myelogenous leukemia cells MV4-11 (IC