Our results described the signature of plasma sEVs from HCC and the upregulated pathway of complement cascades (C1QB, C1QC, C4BPA, and C4BPB) and the coagulation cascade (F13B, FGA, FGB, and FGG), which might be the major factors contributing to the classification of HCC. This evidence concerns the gene C4BPB and hepatocellular carcinoma.