TLR9 and cancer: We applied a combination therapy approach of hydroxychloroquine (HCQ)–sorafenib, both in vitro and in vivo, with data demonstrating the synergistic effect of HCQ in modulating the expression of toll-like receptor (TLR)-9 and regulating the cancer cells stemness, mesenchymal state, autophagy, and sorafenib resistance through inducing the antioxidant superoxide dismutase (SOD)-1 and apoptosis-allied gene expression and reducing the oxidative DNA damage stress in HCC sorafenib-resistant cells via hsa-miR-30a-5p epigenetic regulation axis.