Objective Proteomics were used to analyze changes in the liver protein expression profile of AFLD mice and the effect of resveratrol treatment. Methods The AFLD model of C57BL/ 6J mice was prepared by NIAAA method, and resveratol(400 mg / kg)was administered orally for 9 days. Proteins in the liver tissues were quantified by the 4D non-standard quantitative proteomic method . Under conditions of multiple changes ≥1. 5 or ≤0. 67 and P< 0. 05, significantly up- or down-regulated differentially expressed proteins in three comparison groups were screened. GO classification, KEGG pathway enrichment, and protein network interaction analysis of differentially expressed proteins were carried out. Results Totals of 4513 and 3763 proteins were identified and quantified, respectively, and 1228 differentially expressed proteins and 11 differentially coexpressed proteins were screened. Compared with the control group (P<0. 05), 370 and 324 proteins were significantly down- and up-regulated in the AFLD group. Compared with the AFLD group (P< 0.05), 224 and 227 proteins were significantly up- and down-regulated, respectively, in the resveratrol treatment group. A total of 1228 differentially expressed proteins were involved in 40 biological processes, 36 cellular components, 38 molecular functions, and 45 KEGG pathways annotated by GO classification. A total of 11 differentially coexpressed proteins were screened and found to be related to 9 molecular functions and 5 signaling pathways, of which 4 differentially coexpressed proteins interacted. Conclusions After chronic alcohol intake, the protein expression profile of mouse liver tissue changes significantly. The changes in expression of Sult1b1 (sulfotransferase family cytosolic 1B member 1), Apoa4 (apolipoprotein A-IV), Gpat3 ( glycerol-3-phosphate acyltransferase 3), and Ephx1 ( epoxide hydrolase 1) were closely related to AFLD occurrence and the therapeutic effect of resveratrol on AFLD.