Based on our results and the cell-to-cell communication mediated by sEVs in HCC, we speculate that the liver microenvironment might be modified by liver tumors via specific cargo in sEVs, and the main cargo is C1QB, C1QC, C4BPA, and C4BPB from the complement system. The gene discussed is C4BPA; the disease is hepatocellular carcinoma.