<p>Hepatocellular carcinoma (HCC), which is mostly caused by chronic liver illnesses such as cirrhosis, non-alcoholic steatohepatitis, and viral hepatitis, continues to be one of the major causes of cancer-related death globally. Serum alpha-fetoprotein (AFP) is frequently used for diagnosis; however, because of its poor sensitivity and specificity, new trustworthy biomarkers must be found. According to recent data, glycoproteins show promise as a means of enhancing HCC diagnosis and treatment targeting. Changes in fucosylation and sialylation are examples of aberrant glycosylation that have a significant impact on immunological evasion, tumour development, and metastasis. Key glycoproteins, including hemopexin, endosialin, pentraxin 3, haptoglobin, and ceruloplasmin, are summarised in the current review along with their structural traits, expression patterns, and functions in the pathophysiology of HCC. Although increased haptoglobin glycosylation improves early diagnostic potential, cereuloplasmin increases tumour cell survival by regulating ferroptosis. Endosialin promotes stromal remodelling and immune evasion in the tumour microenvironment, while hemopexin helps control oxidative stress. Pentraxin 3 has a dual, context-dependent activity as a pro-tumorigenic factor and a tumour suppressor. These glycoproteins have the potential to greatly enhance illness stratification and diagnostic accuracy when paired with conventional indicators like AFP. The precise mapping of glycosylation patterns made possible by emerging multi-omics and spatial technologies provides a clearer understanding of their mechanistic functions and translational significance. When combined, glycoprotein-based biomarkers and therapeutic targets offer new possibilities for early identification and individualised HCC treatment, hence representing a potential area for precision oncology.</p>