We found that TRIM65 significantly increased PA levels and that the overabundance of intracellular PA could be secreted into the tumor microenvironment, promoting the switching of TAM to M2 macrophages, and inhibiting the recruitment of CD8+ T cells, which suppressed the immunocidal effect, thus promoting malignant progression of HCC. This evidence concerns the gene TRIM65 and hepatocellular carcinoma.