Abstract： Objective： To explore the mechanism of salidroside in the treatment of liver fibrosis in metabolic dysfunction-associated steatohepatitis （MASH）. Methods：Thirty male C57BL/6 mice were randomly divided into five groups （n=six per group）： the Control group， the model group （CDAHFD group）， the low-dose salidroside group （Sal-L group），the high-dose salidroside group （Sal-H group），and the Sting inhibitor group （C-176 group）. Except for the Control group，all other groups were fed a CDAHFD diet for nine weeks to induce the MASH-related liver fibrosis model. Starting from the 4th week， mice in the Sal-L and Sal-H groups received oral gavage of salidroside at 25 mg/kg and 50 mg/kg，respectively，three times per week. The C-176 group received intraperitoneal injection of the C-176 inhibitor at 15 mg/kg，three times per week. Mice in the Control and CDAHFD groups received oral gavage of an equal volume of normal saline for six weeks. Serum ALT and AST activities，as well as hepatic triglyceride （TG） and hydroxyproline （Hyp） contents were measured using biochemical assay kits. Hepatic steatosis， inflammation， and fibrosis were assessed by HE and Sirius red staining， along with semi-quantitative NAS scoring. Cytosolic mtDNA content was detected by RT-qPCR. Western blot was used to measure the protein expression levels of microtubuleassociated protein 1 light chain 3-Ⅱ/Ⅰ （LC3-Ⅱ/Ⅰ），phosphorylated nuclear factor kappa B （p-NF-κB），cyclic GMP-AMP synthase （cGAS）， phosphorylated stimulator of interferon genes （p-Sting）， tumor necrosis factoralpha （TNF-α），and interleukin-1β （IL-1β）. Results：Compared with the Control group，serum AST，ALT，and TG levels were significantly increased in the CDAHFD group （P＜0.05）. Compared with the CDAHFD group，serum AST， ALT， and TG levels were significantly decreased in the Sal-L， Sal-H， and C-176 groups （P＜0.05）. Compared with the Control group， hepatic α -smooth muscle actin （α -SMA） and Hyp levels were significantly increased in the CDAHFD group （P＜0.05）. Compared with the CDAHFD group，hepatic α-SMA and Hyp levels were significantly decreased in the Sal-L， Sal-H， and C-176 groups （P＜0.05）. Compared with the Control group， the protein expression of cGAS，p-Sting，Sting，p-NF-κB，NF-κB，TNF-α，IL-1β，and cytosolic mtDNA content were significantly increased in the liver of the CDAHFD group （P＜0.05）. Compared with the CDAHFD group，LC3-Ⅱ protein expression was significantly increased （P＜0.05）， while the protein expression of cGAS， p-Sting， Sting， p-NF-κB，NF-κB，TNF-α，IL-1β，and cytosolic mtDNA content were significantly decreased in the Sal-L，Sal-H， and C-176 groups （P＜0.05）. Conclusion： Salidroside alleviates MASH-associated liver fibrosis by activating mitochondrial autophagy in hepatocytes， reducing mtDNA release， and thereby inhibiting the cGAS-Sting inflammatory pathway.