Metabolic-associated fatty liver disease (MAFLD), which was previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. The authors of an article, recently published in Acta Pharmaceutica Sinica B, provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at the protein but not mRNA level.