The occurrence and development of acute myeloid leukemia (AML) is not only related to gene mutations, but also influenced by abnormal epigenetic regulation, in which DNA methylation is one of the most important mechanisms. Abnormal DNA methylation may lead to the activation of oncogene and the inactivation of tumor suppressor gene, resulting in the occurrence of leukemia. The mutations of DNA methylation enzymes associated with AML may have certain characteristics. The AML with recurrent cytogenetic abnormalities is also related to abnormal methylation. Some fusion genes can alter DNA methylation status to participate in the pathogenesis of leukemia. In addition, chemotherapy drug resistance in patients with AML is associated with the change of gene methylation status. Considering the reversibility of the epigenetic modification, targeted methylation therapy has become a hotspot of AML research.