This study not only revealed that HCC cells with upregulated PIWIL1 induced MDSCs transport to the TME and but also demonstrated that HCC cells-derived complement C3 induced by PIWIL1 increased the expression of immunosuppressive cytokine IL-10 in MDSCs by activating p38 MAPK signaling, ultimately leading to HCC malignant progression. This evidence concerns the gene C3 and hepatocellular carcinoma.