A previous study demonstrated that PEPT2 promotes the absorption of dipeptide species in chronic myelogenous leukemia stem cells, activating p38MAPK‐mediated phosphorylation of Smad3, thereby maintaining stem cell activity.[33] Considering that PEPT1 has a similar sequence and substrate as PEPT2, we examined the metabolic changes in PEPT1‐knockdown HCC cells. This evidence concerns the gene SMAD3 and hepatocellular carcinoma.