Here in this study, through bioinformatics analysis and subsequent experimental validation, we found that ZFP36L1 expression was aberrantly decreased in acute myeloid leukemia (AML) patients compared with normal controls and selectively up-regulated during monocyte/macrophage differentiation and facilitated the process by directly binding to AREs in the 3′UTR of CDK6 mRNA, leading to decreased expression of CDK6, which unravels a RBP-mediated regulatory circuit composed of ZFP36L1 and CDK6 and provides a potential target for AML therapy. This evidence concerns the gene CDK6 and acute myeloid leukemia.