Abstract: Glycosylation is an important post-translational modification of proteins; proteins with abnormal O-glycosylation are considered potential markers for malignant tumors. C1GALT1, the core 1β1, 3-galactosyltransferase, is an essential enzyme for the synthesis of the core 1 structure of mucin-type O-glycans. The function of C1GALT1 is to transfer galactose (Gal) to form the Galβ1-3GalNAcαSer/Thr structure. It was found that C1GALT1 played important roles in the development and progression of various malignant tumors such as respiratory, gastrointestinal and urogenital cancers and could regulate O-glycosylation of multiple tumor-associated proteins. Furthermore, C1GALT1 was not only involved in regulating the proliferation, invasion, metastasis, radiotherapy resistance and drug resistance of tumors, but also closely related to the clinical characteristics and prognosis of cancer patients. This review summarizes the recent advances in researches investigating the role of C1GALT1 in malignant tumors and discusses the prospects of using C1GALT1 as a therapeutic target.