Objective:　Steroid-induced　osteonecrosis　of　the　femoral　head　(SONFH)　is　a　debilitating　bone　condition　associated　with　femoral　head　collapse　and　hip　joint　dysfunction.　The　pathogenesis　of　SONFH　is　still　not　fully　elucidated.　This　study　aims　to　explore　the　role　of　mitochondrial　cardiolipin　metabolism　disruption　in　SONFH　and　the　potential　protective　effects　of　simvastatin　(SIM).　Methods:　Osteoblasts　were　cultured　in　vitro　under　high　concentrations　of　dexamethasone　(DEX)　to　mimic　the　effects　of　glucocorticoid　exposure　seen　in　SONFH.　Mitochondrial　structural　changes　and　cardiolipin　distribution　were　examined　using　transmission　electron　microscopy　and　confocal　microscopy.　Osteoblast　proliferation　and　apoptosis　were　assessed　using　CCK-8　assays　and　flow　cytometry.　Mitochondrial　cardiolipin　content　was　quantified　by　ELISA,　while　cytochrome　c　(Cyt-c)　expression　was　measured　through　Western　blotting.　Mitochondrial　staining　with　NAO　was　analyzed　using　confocal　microscopy　and　flow　cytometry.　Results:　DEX　exposure　led　to　mitochondrial　cardiolipin　metabolism　disorder　and　redistribution,　resulting　in　significant　mitochondrial　structural　damage.　This　disruption　was　associated　with　increased　release　of　Cyt-c　into　the　cytoplasm,　which　correlated　with　heightened　osteoblast　apoptosis.　SIM　treatment　mitigated　these　effects,　reducing　osteoblast　apoptosis　by　preserving　mitochondrial　function　and　modulating　cardiolipin　content　and　distribution.　Conclusion:　This　study　demonstrates,　for　the　first　time,　that　glucocorticoid-induced　disruptions　in　mitochondrial　cardiolipin　metabolism　contribute　to　the　pathogenesis　of　SONFH　by　inducing　Cyt-c　release　and　subsequent　osteoblast　apoptosis.　SIM　exerts　a　protective　effect　by　preserving　mitochondrial　integrity　and　function,　offering　a　potential　therapeutic　avenue　for　treating　hormone-induced　osteoblast　damage　in　SONFH.　©　2025　The　Authors