The Chinese Qingrejiedu Decoction (QDD) is a traditional medicine prepared from some herbs. QDD has the potential to treat and manage liver and gallbladder neoplasms. Our main objective is to examine the molecular mechanism network pharmacology and perform bioinformatics research on QDD for the treatment of liver and gallbladder neoplasms. We used Gene Expression Omnibus (GEO) database to obtain GSE106671 expression profiling dataset by array type based on GPL16956 platform. The dataset comprised liver metastatic invasion and metastasis of gallbladder cancers; there were three samples of parental gallbladder cancer cells and three samples of highly metastatic gallbladder cancer cells. We used the Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) to identify targets of QDD in liver and gallbladder neoplasms. All the Protein-protein interaction (PPI) networks were analyzed in STRING and Cytoscape R software. Optimal animal model was determined by Multi-Ontology Enrichment Tool (MOET) enrichment. Our study identified 113 significant differentially expressed genes (DEGs), including 47 up-regulated and 66 down-regulated genes. The PPI network analysis revealed ten hub genes that were essential in the progression of liver and gallbladder neoplasms. The KEGG pathways were enriched in C-type lectin receptor signalling (CLR), Vascular endothelial growth factor (VEGF) signalling, P53 signalling, and nucleotide-binding oligomerization domain (NOD)-like receptor signalling, while the biological pathways were enriched in catabolism and metabolism of collagen, regulation of inflammatory response, cell death, defense response. Overall, Bonobo appears to have the strongest statistical evidence of association between the hub genes and liver cancer. QDD seems to be a significant medicine in treating and diagnosing gallbladder and liver neoplasms.