Due to the ineffective conventional treatment for hepatocellular carcinoma (HCC), the nonviral gene delivery system has been proved to be an attractive alternative to HCC therapy. In this work, we have developed a kind of new self-assembled nanoparticles, which were named as amino-modified silica nanoparticles (AMSNs). Scanning electron microscopy and zeta potential results demonstrated that AMSNs had a diameter of 20-30 nm and positive surface charges of +11.3 mV, respectively. The AMSNs could bind DNA strongly and protect DNA from degradation, which was confirmed by DNA-binding assay and serum protection assay. Furthermore, AMSNs could transfer foreign DNA into targeted cells with high transfection efficiency and little cytotoxicity. Combined with the p53 gene, AMSNs could transfect pp53-EGFP in HepG2 cells and result in a high-level of p53 mRNA and protein expressions. The nude mice treated with AMSNs/pp53-EGFP complexes showed significant tumor growth inhibition. Our results showed the AMSNs, an efficient gene vector, had the potential of gene therapy for HCC.