Objective::To explore the possible mechanisms of Erzhiwan in the treatment of hepatocellular carcinoma (HCC) based on the network pharmacology. Method::The candidate active components and targets of Ligustri Lucidi Fructus and Ecliptae Herba were obtained through retrieval of the traditional Chinese medicine (TCM) systems pharmacology database (TCMSP) and literatures. Through Uniprot database and the human genome database (GeneCards), the overlapping genes of Erzhiwan and hepatocellular carcinoma were collected. The " candidate active components-targets" network of Ligustri Lucidi Fructus and Ecliptae Herba was built with Cytoscape 3.6.0 software. Drug target proteins and disease targets were mapped, and Venn map was drawn by Omicshare database. Major targets interaction network was formed by using String database and " Generate style from statistics" tool in Cytoscape 3.6.0 software. Molecular docking with active components was carried out by Systems Dock Web Site. The Gene Ontology (GO) classification enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the targets were carried out in DAVID database. Result::Totally 21 active components, including beta-sitosterol, quercetin, luteolin, demethylwedelolactone, kaempferol, and 151 targets, including tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), N-terminal kinase (JUN), proto-oncogene (c-MYC), matrix metalloproteinase-9 (MMP-9) of Erzhiwan were collected. Erzhiwan exerts its effects on HCC mainly by acting on signal pathways, including Hepatitis B, TNF, Phosphatidylinositol-3-kinase (PI3K/Akt), tumor suppressor gene p53 and Toll-like receptor. Conclusion::Based on the methodology of network pharmacology, this study preliminarily predicted the major targets and pathways of Erzhiwan in the treatment of HCC, providing a direction for further studies.