Objective To investigate the role of Caveolin-1 (CAV1) in the progression of metabolic-associated fatty liver disease (MAFLD) and its potential mechanisms of action. Methods Based on the human database GSE126848, we identified differential CAV1 expression in normal, obese, and non-alcoholic fatty liver disease (NAFLD) individuals. A CAV1 knockout (CAV1 KO) MAFLD mouse model was established using a 16-week high-fat diet (HFD). Albumin (ALB) and CAV1 co-localization was used to determine CAV1 expression in the liver. CAV1 mRNA and protein levels were detected in primary hepatocytes. Lipid deposition and inflammation were assessed using HE staining, Oil Red O staining, and Nile Red staining. Mitochondrial damage was observed by transmission electron microscopy. Cellular senescence and iron metabolism changes were evaluated by immunohistochemistry for cyclin-dependent kinase inhibitor 1A (P21), dihydroethidium (DHE) staining, and iron staining. Furthermore, a hepatocyte senescence model was constructed and divided into normal, palmitic acid (PA), CAV1-siRNA, and CAV1-GV146 (CAV1 overexpression) groups to analyze lipid deposition, senescence, and Fe2+ levels. Western blot, qRT-PCR, and mitochondrial membrane potential (JC-1) assays were used to further validate the effect of CAV1 on hepatocyte senescence and mitochondrial function. Results In vivo experiments showed that CAV1 KO exacerbated lipid deposition, inflammation, and liver senescence. This was evidenced by enhanced lipid staining, increased levels of senescence markers including histone H2A variant X phosphorylation (γ-H2AX), cyclin-dependent kinase inhibitor 2A (P16), and P21, decreased levels of oxidative stress markers glutathione (GSH) and superoxide dismutase (SOD), increased malondialdehyde (MDA) and reactive oxygen species (ROS), and mitochondrial shrinkage with increased mitochondrial membrane density. Iron metabolism analysis revealed that CAV1 KO led to decreased Fe3+ and increased Fe2+ accumulation, which was associated with the nuclear receptor coactivator 4-ferritin heavy chain 1 (NCOA4-FTH1) pathway. Supplementation with the CAV1 scaffolding domain (CSD) significantly improved the reduction of Fe3+ and the accumulation of Fe2+. In vitro, silencing CAV1 promoted lipid accumulation, mitochondrial damage, and cellular senescence. This was accompanied by elevated ROS levels, Fe2+ accumulation, decreased NCOA4 expression, and increased FTH1 expression. Conversely, CAV1 overexpression attenuated these effects. Immunofluorescence revealed that CAV1 silencing enhanced NCOA4 and FTH1 co-localization, an effect reversed by CAV1 overexpression. Importantly, deferoxamine (DFO) treatment reduced ROS levels and ameliorated senescence induced by CAV1 silencing. Collectively, these results indicate that CAV1 modulates liver senescence, potentially via the NCOA4-FTH1 pathway. Conclusion Caveolin-1 can slow down MAFLD hepatocyte senescence, possibly by regulating iron homeostasis through the NCOA4-FTH1 pathway.