The present study demonstrates the synergistic interaction of ramucirumab with sorafenib to invoke a strong anticancer activity against hepatocellular carcinoma by inducing apoptosis; inhibiting cell growth/proliferation; upregulating the expression of CASPASE3; downregulating the expression of MMP-9, EGFR and VEGFR2 and decreasing pSTAT3 and pVEGFR2 protein levels in HepG2 cancer treated cells. This evidence concerns the gene EGFR and hepatocellular carcinoma.