Proteomic data and <i>in vitro</i>/<i>in vivo</i> experiments demonstrated that NPLOC4 inhibits the type I interferon pathway in TAMs, promotes M2 polarization, and suppresses CD8<sup>+</sup> T-cell infiltration, thereby creating an immunosuppressive microenvironment in HCC. This evidence concerns the gene CD8A and hepatocellular carcinoma.