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Artesunate (ART), a water-soluble derivative of artemisinin, has been reported to exert antineoplastic effects via diverse mechanisms in various types of cancer. Therefore, understanding the underlying mechanism of action of ART in distinct cancer types is indispensable to optimizing the therapeutic application of ART for different types of cancer. The present study aimed to investigate the cellular and molecular mechanisms responsible for the antineoplastic effects of ART in diffuse large B cell lymphoma (DLBCL) cells. Cell proliferation was measured using Cell Counting Kit-8 and colony formation assays. The levels of apoptosis and cell cycle distribution were investigated using flow cytometry. In addition, western blotting was used to analyze the expression levels of ART-induced apoptosis-, autophagy- and ferroptosis-related proteins. Monodansylcadaverine staining was performed to determine the levels of autophagy. Moreover, malondialdehyde and reactive oxygen species assays were used to determine the levels of ferroptosis. The results of the present study revealed that ART inhibited proliferation, and induced apoptosis, cell cycle arrest, autophagy and ferroptosis in DLBCL cells. Pharmacological inhibition of autophagy and ferroptosis alleviated the increased levels of apoptosis induced by ART. Notably, ART was found to exert its effects via inhibition of STAT3 activation. The genetic knockdown of STAT3 enhanced ART-induced autophagy and ferroptosis, and concomitantly upregulated the expression levels of apoptosis- and cell cycle-related proteins. In conclusion, the findings of the current study suggested that ART may induce apoptosis and cell cycle arrest to inhibit cell proliferation, and regulate autophagy and ferroptosis via impairing the STAT3 signaling pathway in DLBCL cells. • Artesunate induces apoptosis, cell cycle arrest, autophagy and ferroptosis in DLBCL cells • Inhibition of autophagy alleviates Artesunate-induced apoptosis in DLBCL cells • Ferroptosis Inducer exerts synergistic effect with Artesunate in DLBCL cells • Artesunate induces autophagy and ferroptosis in DLBCL cells by impairing STAT3 signaling [ABSTRACT FROM AUTHOR]