Finally, the top five hub genes osteopontin (SPP1), Collagen alpha-2(I) chain (COL1A2), Insulin-like growth factor I (IGF1), lipoprotein A (LPA), and Galectin-3 (LGALS3) were identified from the protein–protein interaction (PPI) network and those highly altered genes were validated by western blot assay and Immunohistochemistry (IHC) analysis and found to be associated with clinical outcome of HCC patients. Here, SPP1 is linked to hepatocellular carcinoma.