In the present study, we demonstrated that miR-15a-5p prevented basal and DNR-induced autophagy in AML by directly downregulating four genes involved in this catalytic process: ATG9A, GABARAPL1, ATG14, and SMPD1. Thereby, miR-15a-5p might prevent autophagy by inhibiting different phases: initiation, elongation and autophagosome formation, fusion, and autolysosome formation. The gene discussed is SMPD1; the disease is acute myeloid leukemia.