In our study, we focused on the potential association between CREB3L4 and PI3K/AKT/mTOR pathway in the HCC pathogenesis as it is constitutively activated in a significant proportion of HCC patients, together with significant upregulation in the HCC tissues compared with the adjacent tissues according to our clinical experience and bioinformatic analysis. This evidence concerns the gene CREB3L4 and hepatocellular carcinoma.