Hepatocellular carcinoma (HCC) mortality rates have risen significantly in recent years. Folium Artemisiae Argyi (FAA) has demonstrated anticancer properties, yet its specific mechanisms of action in HCC treatment remain unclear. This study used network pharmacology and molecular docking to investigate these mechanisms. HCC-related targets were sourced from GeneCards, NCBI, and GEPIA2 databases, while active FAA compounds and targets were identified through Swiss Target Prediction. Protein-protein interaction (PPI) networks were constructed using the STRING database and visualized with Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using ShinyGO. Autodock was employed for molecular docking, and gene expression profiling was performed to assess the prognosis and survival of HCC patients. The study identified 19,467 predicted HCC targets and 292 FAA compound targets, with 207 overlapping targets. GO/KEGG enrichment analyses indicated that FAA influences HCC by regulating biological processes related to cell proliferation and survival, particularly through pathways such as cancer pathways, proteoglycans in cancer, and the PI3K-AKT pathway. Key targets identified included AKT1, SRC, EGFR, PPARG, ESR1, BCL2, PTGS2, HSP90AA1, HIF1A, and MAPK3, with most showing upregulation linked to poor prognosis, reduced disease-free survival, and lower overall survival in HCC patients. Molecular docking analysis confirmed strong interactions between the top five core targets and FAA compounds. Among them, Quercetin, Mandenol, and Ethyl Oleate demonstrated high binding affinities with EGFR, scoring -7.98 kcal/mol, -7.17 kcal/mol, and -6.97 kcal/mol, respectively. In contrast, (R)-Naringenin showed the strongest interaction with AKT1, exhibiting a binding affinity of -8.51 kcal/mol.These findings suggest that FAA exerts a therapeutic effect on HCC via multipathway pharmacological mechanisms, offering the potential to improve patient outcomes. The study provides a foundation for clinical validation and the development of novel anti-cancer drugs.