Demethylation belongs to the category of epigenetics. Due to numerous studies, many oncogenes are found to be abnormally highly methylated in MDS patients, leading to functional inactivation of these key genes and loss of control over oncogenes, resulting in morbidity. Based on this theory, demethylation therapy has been proposed and has been clinically effective. The current demethylation drugs are 5-azacytidine (AZA) and 5-azacytidine-2-deoxycytidine (Decitabine) which reduce the overall intracellular DNA methylation and trigger altered gene expression. Both drugs have demethylation effects at low doses and cytotoxic effects at high doses. specific dosing regimens for AZA and decitabine in the treatment of MDS are still being optimized. Patients with high-risk MDS are suitable candidates for the application of demethylating drugs; patients with low-risk concomitant severe hematocrit and/or transfusion dependence are also suitable candidates for demethylating drug therapy. Increasing the course of therapy may improve the efficiency of AZA or decitabine treatment. AZA: AZA 75 mg/m2 subcutaneously or intravenously for 7 d for 28 d is the current recommended regimen for high-risk patients with MDS. AZA significantly improves quality of life, reduces the need for transfusion, and significantly delays the conversion to AML or death in high-risk MDS patients. AZA improves survival even when patients do not achieve complete remission. On the premise that the toxicity is tolerated and the peripheral blood count indicates no progression, those who do not improve after 6 courses of AZA treatment are switched to other drugs. Decitabine: The recommended regimen for decitabine is 20 mg m–2 d–1 intravenous infusion over 5 d for 4 weeks. Most patients start at the end of the second course of treatment and achieve optimal results at the same time point. Decitabine is usually administered in adequate doses for 3–4 courses before termination of therapy is considered. In China, decitabine has been in clinical use for almost 3 years, and hematologists around the world continue to explore better ways to use and dose the drug to achieve better efficacy and maintenance. 5-Azacitidine will also be available. For intermediate-to-high risk MDS, in addition to traditional chemotherapy and other new approaches still in development, demethylation therapy is a relatively mild and effective treatment.