These findings, together with our results that PSMA5 expression was upregulated in HCC, prompted us to make a presumption that PSMA5 in HCC cells was transferred by HCC cell‐derived exosomes into macrophages to drive M2 polarization via activating the JAK2/STAT3 pathway, thereby exerting an oncogenic effect on HCC cells. This evidence concerns the gene JAK2 and hepatocellular carcinoma.