Hepatocellular carcinoma (HCC) still remains a global health challenge as it shows genetic heterogeneity and limited therapy response. In a new study, the cellular responses in HCC that accompany the nearly universal repression of urea cycle enzymes and consequent arginine auxotrophy were investigated, since previous findings demonstrated that that HCC consistently represses urea cycle gene expression and thus become auxotrophic for exogenous arginine becoming severe disease.