Non-alcoholic steatohepatitis (NASH) is considered a progressive stage of non-alcoholic fatty liver disease (NAFLD) that can progress to cirrhosis and hepatocellular carcinoma. ACT001 is a novel sesquiterpene lactone derivative that has been shown to have significant antitumor and anti-inflammatory effects. However, the effect of ACT001 on NASH is unclear.Methionine- and choline-deficient (MCD) diet was fed to C57BL/6J mice for 6 weeks to induce the NASH model.iTRAQ quantitative proteomic analysis was performed to clarify the expression of differential proteins (DEPs) after ACT001 action.381 DEPs, including 162 up-regulated and 219 down-regulated proteins, were identified between the model and ACT001 high-dose groups.the function of DEPs in the proteome and the signaling pathways involved will provide new ideas for the research of new drugs for NASH treatment.