Using STING- (Tmem173−/−) and cGAS-knockout (Mb21d1–/–) mouse tumor models, we confirmed that the gut microbiome regulates RT sensitivity in HCC via cGAS–STING signaling in dendritic cells (DCs), which in turn, modulate host cytotoxic T lymphocyte responses. This evidence concerns the gene STING1 and hepatocellular carcinoma.