Objective To investigate the therapeutic effects of Qushi Huoxue decoction on a mouse model of metabolic dysfunction-associated steatotic liver disease （MASLD） and to explore its underlying mechanism associated with the NF-κB/Bcl-2 signaling pathway. Methods MASLD was induced in mice by feeding them a high-fat diet for 12 weeks， while the control mice were fed a standard diet. After successful modeling， the treatment groups were given low， medium， and high doses of Qushi Huoxue decoction for 6 weeks. Hepatic lipid deposition and inflammatory infiltration were evaluated using hematoxylin–eosin （HE） and oil red O staining. The serum levels of ALT， AST， TG， TNF-α， IL-6， and IL-1β， as well as the hepatic levels of MDA， GSH-Px， and SOD， were measured with commercial assay kits. The hepatocyte apoptosis rate was determined by TUNEL assay， and the mRNA expression levels of apoptosis-related genes were measured by RT-qPCR. The protein expression levels of Bcl-2， Bax， and Caspase-3 in liver tissues were detected through immunohistochemistry and Western blot. Results Qushi Huoxue decoction significantly alleviated hepatic lipid deposition， oxidative stress， inflammatory response， and hepatocyte apoptosis. It led to a reduction in the serum levels of ALT， AST， TG， TNF-α， IL-1β， and IL-6， a decrease in the hepatic MDA level， and an increase in the hepatic GSH-Px and SOD levels （P < 0.05， P < 0.01）. Moreover， it also downregulated the protein expression levels of p-NF-κB/NF-κB， Bax， and Caspase-3 in the liver （P < 0.05， P < 0.01）， as well as the mRNA expression levels of Bax and Caspase-3， while upregulating the Bcl-2 mRNA expression （P < 0.05， P < 0.01）. Conclusions Qushi Huoxue decoction effectively enhances liver function， optimizes lipid metabolism， alleviates oxidative stress， and mitigates inflammatory responses in mice with MASLD， consequently decreasing hepatocyte apoptosis. These effects are potentially mediated via the modulation of the NF-κB/Bcl-2 signaling pathway.