The effective analysis of glycoproteomics in clinical complex samples is of vital importance for the diagnosis and therapy of diseases. In this study, a hydrophilic MOFs-303-functionalized magnetic probe (GO@Fe3O4@MOF-303) is designed and fabricated to profile N-linked glycopeptides. Owing to its strong magnetic property, large surface area (845 m2 g-1), excellent hydrophilicity and suitable porous structure, the GO@Fe3O4@MOF-303 probe exhibits an ultralow detection limit (0.1 fmol μL-1), perfect size-exclusion effect (HRP digests/BSA protein/HRP protein, 1 : 1000 : 1000, w/w/w), a high binding capacity (200 mg g-1) and excellent reusability in the capture of standard N-linked glycopeptides. More excitingly, the GO@Fe3O4@MOF-303 probe also shows remarkable performance in practical applications, where 274 N-linked glycopeptides from 101 glycoproteins were identified in total for healthy controls, while a total of 265 N-linked glycopeptides from 102 glycoproteins were identified in serum (1 μL) with hepatocellular carcinoma (HCC). In addition, we discovered 4 up-regulated and 19 down-regulated serum glycoproteins in HCC patients by the hierarchical clustering heatmap. All results demonstrated that the reusable GO@Fe3O4@MOF-303 probe has great potential in profiling different N-linked glycopeptides in complex clinical samples. This study not only developed a novel probe for the highly effective capture of N-linked glycopeptides but also contributed to further understanding the mechanism of HCC and provides guidance for the development of novel clinical diagnostic methods.