The HMGB1–RICTOR “RNA–RNA” crosstalk network facilitates glutamine metabolism in HCC cells via activating a positive feedback loop involving mTORC2-AKT-C-MYC to upregulate GS expression, also inducing mTORC1 signaling to derepress SIRT4 effects on GDH expression. Here, HMGB1 is linked to hepatocellular carcinoma.