To identify the functionally essential amino acids and regions of METTL16 for its interaction with eIF3a/b and for HCC cell survival, we performed high-density CRISPR screen to generate the CRISPR gene tiling scan structure of METTL16 and predicted the protein–protein interaction (PPI) models between METTL16 and eIF3a/b accordingly. This evidence concerns the gene METTL16 and hepatocellular carcinoma.