O-GlcNAcylation is a post-translational modifications regulating dynamic intracellular signaling by two enzymes, OGT and OGA, which add and remove the modification, respectively. In many types of cancer cells, O-GlcNAcylation is elevated and contributes to the transformed phenotypes, but the molecular mechanisms is not fully understood. In this study, we examined O-GlcNAcylation-mediated cancer cell proliferation focusing on FOXM1 oncogenic transcription factor to regulate cell cycle. Elevated O-GlcNAcylation promoted cell proliferation in MKN45 gastric cancer cells, accompanying with increasing FOXM1 nuclear localization. FOXM1 was not O-GlcNAcylated, but was polyubiquitinated, which was reduced by elevated O-GlcNAcylation. We found some molecules involved in FOXM1 proteasomal degradation which are regulated by O-GlcNAcylation. One is GSK-3β Ser/Thr kinase mediating FOXM1 phosphorylation to induce the ubiquitination (Ub). Elevated O-GlcNAcylation reduced GSK-3β activity following increased FOXM1 protein. The other is FBXL2 ubiquitin E3 ligase mediating FOXM1 Ub. Elevated O-GlcNAcylation reduced FBXL2 protein via increased its Ub. These data suggest that O-GlcNAcylation-mediated FOXM1 stabilization could promote cancer progression.