Inflammation plays fundamental role in hepatocellular carcinoma (HCC) initiation, progression and metastasis. The over expression of pro-inflammatory factors like Tumor necrosis factor-α (TNF-α), selectin, (IL)-6, nuclear factor-κB, TGF-β can alter the hepatic microvasculature. Natural products such as polyphenols, alkaloids, flavonoids, and flavonols have the ability to interface microenvironment of carcinogenic tissue. In the current study we have established human protein interaction network (HPIN) composed of 21 queries (inflammatory proteins related to HCC) and more than 493 neighboring proteins. This interaction provides some potent receptors for docking of plant based immunosuppressant with pro-inflammatory proteins. We have selected eighteen herbal compounds and docked with receptors (ALDH1, TGFBR1, and P2RY2) using Schrodinger software. The study suggests an integrated approach to normalize the immunological dysregulation for HCC treatment through silibinin, leonurine and quercetin.