Abstract: NSD3 is a member of the nuclear receptor-binding SET domain (NSD) family of histone lysine methyltransferases (HKMTases), which play important roles in tumorigenesis. Many recent studies have shown that NSD3 can promote the occurrence of various malignant tumors such as breast cancer, acute myeloid leukemia, NUT midline cancer, and lung cancer. It can fuse with NUP98 and NUT, or interact with BRD4, CHD8, and MYC to form carcinogenic complexes. It can also accelerate cell cycle progression and promote tumorigenesis by regulating the levels of H3K36me2 or EGFR (K721) methylation. NSD3 is not only involved in the occurrence of tumors but also related to the poor prognosis and enhanced invasive ability of tumors. In this paper, the current progress of research regarding NSD3 is summarized and the role of NSD3 in tumorigenesis and its potential application prospects are explored.