In spite of the number of the currently used biomarkers to assess HCC occurrence in NAFLD patients, such as alpha-fetoprotein (AFP), alone or in combination with additional tissue and serum markers, Osteopontin, Glypican-3 (GPC-3), Hyaluronic acid, Laminin, VEGF [18–22], and so forth, their usefulness still remains limited due to lack of sensitivity, specificity, and predictive values for a wide population screening. This evidence concerns the gene GPC3 and metabolic dysfunction-associated steatotic liver disease.