ObjectiveTo summarize the latest research progress on the copper death mechanism in metabolic associated fatty liver disease (MAFLD) and to provide references for the treatment of MAFLD. MethodsWe reviewed recent domestic and international research on copper and copper death in MAFLD, and summarized the role of copper death mechanisms in the pathogenesis of MAFLD and related treatments. ResultsCopper death is primarily caused by abnormal intracellular copper accumulation binding to acylated proteins in the tricarboxylic acid cycle, leading to protein oligomerization, downregulation of iron-sulfur cluster protein expression, triggering a toxic stress response, and ultimately cell death. The occurrence and progression of MAFLD are closely associated with genes associated with the copper death pathway. Imbalanced copper metabolism can lead to insulin resistance, causing abnormalities in blood glucose and lipid metabolism, promoting fat accumulation in the liver, and ultimately contributing to the development of MAFLD. Targeting genes involved in the copper death pathway can delay the progression of MAFLD. ConclusionsThe occurrence and progression of MAFLD are closely linked to the copper death signaling pathway, with copper metabolism imbalance as a core component. This pathway not only directly leads to hepatocyte death but also triggers insulin resistance and abnormal lipid metabolism, jointly driving the progression of MAFLD. Therefore, targeted regulation of the copper death pathway is a therapeutic strategy to slow the progression of MAFLD.