Hepatocellular carcinoma (HCC) is a life-threatening disease. Due to the lack of reliable diagnostic biomarkers, the diagnosis of this disease is challenging. Recently, plasma glycoproteomics has emerged as a powerful tool for the identifying disease diagnostic biomarkers. Here, we performed a comprehensive proteomic and glycoproteomic analysis in the plasma of 12 HCC patients and 12 healthy control (HC) individuals. We identified 20 signature proteins and 32 signature IGPs that can distinguish HCC from HC effectively. Moreover, we demonstrated that IGPs profiles could be better predictive biomarkers for screening HCC than protein profiles. Pathways for signature proteins and IGPs were illustrated. For the first time, we showed that the protein expression level of LGALS3BP, as well as its N-linked glycosylation at the N511/398 sites could be a valuable diagnosis biomarker of HCC. Overall, our data suggest a major role for glycoproteomics in understanding HCC, and presents a number of new biomarkers for future