A tRF-3 from tRNA-Leu-CAG induces apoptosis via binding to ribosomal protein S28 (RPS28) and RPS15, and tRF-3 targets the coding sequence (CDS) and 3′-UTR of RPS28 mRNA, enhances RPS28 expression, and increases 40S ribosomal subunits in hepatocellular carcinoma in mice. Here, RPS28 is linked to hepatocellular carcinoma.