Conforming to this presumption, in our study, PSMA5 knockdown in HCC cells led to the downregulation of PSMA5 in exosomes derived from these HCC cells, and HCC cell‐derived exosomes induced M2 polarization and JAK2/STAT3 pathway activation in macrophages and enhanced the migratory and invasive capabilities of HCC cells. The gene discussed is STAT3; the disease is hepatocellular carcinoma.