Based on network pharmacology and molecular docking technology, the mechanism of radix angelicae sinensis-radix salviae miltiorrhizae drug pair (ASM) in the treatment of acute liver injury (ALI) was studied and verified by experiment. Inthis study, network pharmacology and molecular docking methods were used to screen the core targets of ASM in the treatmentof ALI, and the core targets were enriched by analysis, and protein interaction network was constructed. The core target was molecular docked with the active components of ASM, and the molecular docking was verified by constructing ALI rat model anddetecting the expression of relevant serum biochemical indexes and liver proteins. The results showed that 67 active ingredients were obtained from ASM, of which 75 targets interacted with acute liver injury. Protein-protein interactions (PPI) networkanalysis showed that TP53, CASP3, JUN, STAT3, AKT1, VEGFA, TNF, IL-6, MMP9 and PTGS2 may be the key targets ofASM in the treatment of ALI. The core targets of GO and KEGG signaling pathway enrichment analysis were mainly concentrated in hepatitis B signaling pathway, lipid and atherosclerosis, AGE-RAGE, and apoptosis signaling pathways. Moleculardocking results showed that the core targets (TP53 and CASP3) had good binding sites with β-sitosterol, baicalin and cryptotanshinone. The results of in vivo experiments showed that ASM could reduce the expression levels of ALT, AST and MDA in serum of CCl4-induced model rats, and increase the activity of SOD, CAT and GSH in liver, thereby alleviating the CCl4-inducedoxidative stress. The ASM could up-regulate BCL2 and down-regulate the expression levels of BAX, CASP3 and TP53. Theresults of this study indicate that ASM can effectively ameliorate ALI, which may be achieved through β-sitosterol, baicalin andcryptotanshinone and other chemical components, acting on key targets such as TP53 and CASP3, and through multiple signaling pathways such as p53 signaling pathway and apoptosis pathway. This study provides theoretical and experimental basis forclinical ASM treatment of ALI, and provides new ideas and methods for further research and development of traditional Chinese medicine.