Abstract: Epigenetics refers to the processes that cellular phenotype is affected by modifications and structural changes in DNA, RNA, and histone, but without changes in DNA sequences. Recently, as functions of epigenetic in some biological processes have been revealed, people gradually recognize that epigenetic dysregulation is closely correlated with tumorigenesis and cancer progression, which provide a solid foundation for the development of anti-tuomor epigenetic drugs. Several epigenetic drugs, including small molecule inhibitors targeting epigenetic regulators like writers, erasers, and readers, have been approved in the past decade. However, problems have emerged in the development of new epigenetic anticancer drugs. For example, drug types and their clinical applications are still limited. In this review, the latest advances in epigenetic antitumor drug development have been introduced and clinical application of promising epigenetic antitumor compound shave been listed. In addition, we also analyze the dilemma and explore future evelopment and application strategies for new epigenetic antitumor drugs.