Abstract: The mixed lineage leukemia (MLL) gene, a mammalian homolog of the drosophila histone lysine N-methyltransferase 2(KMT2) gene, encodes a methyltransferase that specifically targets lysine 4 of histone H3 (H3K4). There are six members of MLL protein family (MLL1, MLL2, MLL3, MLL4, SETD1A, SETD1B), which are important epigenetic regulators in mammalian development and play an important role in proliferation and differentiation of hematopoietic stem cells. MLL mutations are closely related to the occurrence of hematologic malignancies and often indicate poor prognosis. Deep understanding the abnormal changes of MLL and its mechanism of action are helpful for the diagnosis of related tumors, the development of targeted drugs and the prognosis. This article focused on the MLL gene and its research progress in hematologic malignancies.