At a low dose of sorafenib, sunitinib, and minimum concentration of AFP-siRNA, the combination of AFP-siRNA-encapsulated PLGA nanoparticles and angiogenesis inhibitors have a synergistic effect on silencing AFP expression and antiproliferation, leading to a significant decrease in cell survival on HepG2 cancer cells without the induction of caspase 3/7 activity. This evidence concerns the gene CASP3 and cancer.