The identification of specific biomarkers within EVsnot only signals the presence of HCC but also provides crucial insightsinto disease progression. SiEV, numerousEV surface proteins, including TENM2, ITGA1, CD36, DSC1, TIMP2, andMUC1, showed good diagnostic performance for liver cancer, with thehighest AUC value being 0.988. In addition,CD63, GPC3, EpCAM, CD113, and CD147 have been analyzed as potentialprotein biomarkers in EVs for HCC detection. This evidence concerns the gene TIMP2 and hepatocellular carcinoma.