Updated project metadata. While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), its heterogeneous glycoproteome and dynamics with disease progression remain unmapped. Employing an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics on resected OSCC tissues, we firstly profiled the N-glycome that overall displayed uniform expression in OSCC patients with (N+, n = 19) and without (N0, n = 12) lymph node metastasis, suggesting relatively stable N-glycosylation during metastasis. Notably, glycoproteomics and advanced correlation analysis uncovered altered site-specific N-glycosylation and associations with clinicopathological features. Importantly, targeted analyses of the multi-omics data unveiled two N-glycans and three N-glycopeptides that were closely associated with patient survival. This study provides novel insight into the complex OSCC tissue N-glycoproteome forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glyco-markers for OSCC.