Mitochondria of hepatocellular carcinoma cells release mtDNA into the cytoplasm in response to ROS, activating Toll-like receptors (TLRs), of which TLR9 can induce CCL2 to recruit macrophages to the TME.Additionally, TLR9 activation can also contribute to the maintenance of the M2 phenotype of TAMs (38). This evidence concerns the gene TLR9 and hepatocellular carcinoma.