Objective: To investigate the impact of RGD peptide (TyrRGD) modified gold nanoparticles (GNPs) conjugated to VEGF siRNA (TyrRGD-GNPs-VEGFsiRNA) on damaging effect of radiofrequency ablation (RFA) for rabbit VX2 tumor. Methods: Rabbit models of VX2 liver were established by direct implantation of VX2 tumor fragment into the liver via laparotomy. Firstly, 6 liver tumor-bearing rabbits were equally divided into 2 groups and underwent injection of TyrRGD-GNPs-VEGFsiRNA or naked GNPs respectively, and the collection and distribution of the two substances in the tumor samples were detected by transmission electron microscopy 48 h after injection. Next, 30 liver tumor-bearing rabbits were equally divided into 3 groups and underwent RFA treatment 48 h after injection of TyrRGD-GNPs-VEGFsiRNA, naked GNPs or normal saline, respectively, and the tumor specimens were harvested 48 h later, after which, pathological observation was performed, the ablation volume of the tumor was measured and the apoptosis in the residual cancer was detected by TUNEL staining. Finally, 27 liver tumor-bearing rabbits were equally divided into 3 groups and underwent treatment of RFA plus TyrRGD-GNPs-VEGFsiRNA injection, RFA plus normal saline injection or normal saline injection only, and then were fed until they naturally died and the survival times were recorded. Results: The accumulation of TyrRGD-GNPs-VEGFsiRNA in the tumor was significantly greater than that of naked GNPs (14.2/500-nm field vs. 0/500-nm field, P<0.01). The ablation volume by RFA after injection of TyrRGD-GNPs-VEGFsiRNA was significantly larger than that after injection of either naked GNPs or normal saline (5.12 cm3 vs. 1.78 cm3 vs. 1.49 cm3, P<0.01), moreover, the cell number of apoptosis in the residual cancer in the former was significantly higher than those in the two latter groups (111.7 vs. 36.3 vs. 34.7, P<0.01), but both above two parameters showed no statistical difference between the two latter groups (both P>0.05). The mean survival time for liver tumor-bearing rabbits undergoing RFA plus TyrRGD-GNPs-VEGFsiRNA injection was significantly prolonged compared with those undergoing RFA plus saline injection or normal saline injection only (70.9 d vs. 51.2 d vs. 43.9 d, P<0.01). Conclusion: TyrRGD-GNPs-VEGFsiRNA can targetedly aggregate in liver tumor, and it also has the effect of expanding the extent of RFA damage and promoting the apoptosis of the tumor cells, and thereby enhance the efficacy of RFA treatment.