AFP and hepatocellular carcinoma: Moreover, we discovered that overexpression of GPC-3 was more likely found in HBV infection, late tumor stage, and microvascular invasion groups and causes shorter overall survival and disease free survival, which means poor prognosis.<h4>Conclusion</h4>GCP-3 could be used as a biomarker in HCC diagnosis and prognosis, especially in evaluated diagnostic value in combination with AFP or GP73, and in forecasting worse survival data of overexpression GPC-3.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022351566].