Hepatic steatosis, inflammation, and fibrosis are the hallmarks of metabolic-associated steatohepatitis (MASH), a serious health risk. This study emphasizes how important gelsolin (GSN) is to the pathophysiology of MASH. The results show that GSN is significantly overexpressed in both MASH patients and animal models. Under MASH models, Gsn knockout (KO) (Gsn) mice demonstrate exacerbated hepatic steatosis, inflammation, and fibrosis, underscoring GSN's protective function. Remarkably, adeno-associated virus (AAV)-mediated restoration of Gsn substantially alleviates these pathological features, indicating its therapeutic potential. Mechanistically, the absence of GSN leads to increased F-actin polymerization and heightened activation of Yes-associated protein (YAP), thereby intensifying the inflammatory response. Subsequently, the experimental data identify a co-expression relationship between GSN and MDM2, and GSN is found to facilitate the ubiquitination and subsequent degradation of P53 via MDM2, a crucial process for liver protection. These findings imply that GSN is essential for controlling important molecular pathways in MASH by encouraging P53's MDM2-mediated degradation, which lessens the severity of hepatic steatosis. The research offers important new understandings of the molecular mechanisms of MASH and suggests GSN as a viable therapeutic target to reduce liver damage and preserve hepatic homeostasis.