In the current study, we discussed the influence of ferroptosis on NASH and discovered a meaningful role of HO-1 in ferroptosis using hepatocyte conditional HO-1 knockout (HO-1HEPKO) mice, HO-1 knockdown and overexpression cells, and NASH patients, revealing HO-1 as a hopeful target for the prevention and treatment of hepatic steatohepatitis by inhibiting ferroptosis. Here, HMOX1 is linked to metabolic dysfunction-associated steatohepatitis.