HepatoCellular Carcinoma, being one of the most mortally convoluted malignancy with mounting number of occurrences across the world and being classified as the third most prevalent cause of cancer-associated mortalities and sixth most prevalent neoplasia. The active phytoconstituent andrographolide, derived from Andrographis paniculata is conveyed to reconcile a number of human ailments including various oncologies. However, the molecular mechanism underlying the anti-oncogenic effects of Andrographolide on HCC remains skeptical and unclear, emerging as a budding challenge for researchers and oncologists. The present study intends to analyze the underlying pharmacological mechanism of Andrographolide over HCC, established via assimilated approach of network pharmacology. Herein, the Network pharmacology stratagem was instigated to investigate potential HCC targets. The Andrographolide targets along with HCC targets were extracted from multiple databases. A total of 162 potential overlapping targets among HCC and Andrographolide were obtained and further subjected to gene ontology and Pathway enrichment analysis by employing OmicsBox and DAVID database, respectively. Subsequently, Protein-protein interaction network construction by Cytoscape software identified the top 10 hub nodes which were validated by survival and expression analysis. Further, the results derived from molecular docking and dynamic simulations by CB-Dock2 server and Desmond module (Schrodinger software) indicate ALB, CCND1, HIF1A, TNF, and VEGFA as potential Andrographolide related targets with high binding affinity and promising complex stability. Our findings not only reveal the antioncogenic role of andrographolide but also provide novel insights illuminating the identified targets as scientific foundation for anti-oncogenic clinical application of andrographolide in HCC therapeutics.Communicated by Ramaswamy H. Sarma.