Peptides have been extensively studied in nanomedicine with great bioactivity and biocompatibility; however, their poor cell-membrane-penetrating properties and nonselectivity greatly limit their clinical applications. In this study, tumor-targeting therapy was achieved by modifying our previously developed efficient peptide vector with the cancer-targeting peptide RGD, enabling it to specifically target tumor cells with a high expression of RGD-binding receptors. B-cell lymphoma-2 antisense oligonucleotides were selected as the target model to validate the effectiveness of the delivery carriers. Results demonstrated that this delivery system can be efficiently and selectively taken up by RGD receptor-positive cells (αvβ3 integrin receptor), further inducing effective target gene knockdown. Overall, this system provided a promising strategy for the targeted delivery of nucleic acid drugs.