Mechanistically, tRF5-GlyGCC can interact with KDM6B to epigenetically upregulate Runx2 and then transcriptionally activate ITGBL1 and S100A9 expression in HCC cells, which further reduces NK cell cytotoxicity directly and attracts myeloid-derived suppressor cell (MDSC) to inhibit NK cell function indirectly, respectively. Here, RUNX2 is linked to hepatocellular carcinoma.