Recent studies suggest that Elevated O-GlcNAcylation by increased O-GlcNAc transferase (OGT) and/or decreasing O-GlcNAcase (OGA) levels is associated with cancer initiation, progression, invasion, and metastasis. However, the function of OGT in colon cancer tumorigeneses remains unclear. Here, we showed OGT expression is elevated in human colon cancer tissue compared with adjacent normal tissue, and cases with higher OGT expression had shorter survival time. Additionally, OGT mRNA expression was positively correlated with pathologic TNM stage from TCGA public database. Finally, we found knock-down of OGT expression by RNA interference inhibits cell proliferation, migration and invasion in colon cancer cell lines. Taken together, this study imply that elevated OGT expression had an important function in colon cancer formation and progression, and OGT may be a valuable prognostic factor and therapeutic target., Competing Interests: None., (IJCEP Copyright © 2019.)