Most anticancer agents induce cancer cell death; however, multidrug-resistant cancers often lead to treatment failure. The effective use of curcumin as an anticancer agent has been demonstrated in clinical trials. Tetrahydrocurcumin, a major curcumin metabolite, exhibits pharmacological activities similar to those of curcumin. Curcumin induces cell death mainly through the apoptosis pathway, and tetrahydrocurcumin induces cell death mainly via an autophagy pathway in HL60 cells. Here, we investigated whether curcumin and tetrahydrocurcumin can induce apoptosis-and autophagy-mediated cell deaths in Ara-C-resistant cancer cells, respectively. The results demonstrated that curcumin and tetrahydrocurcumin induced cell death by apoptosis and autophagy, respectively, in Ara-C-resistant HL60 cells. Thus, curcumin and tetrahydrocurcumin have potential applications in the treatment of acute myeloid leukemia with Ara-C resistance.