Nanotechnology and drug co-delivery offera novel avenue in drug delivery research liposome-based co-delivery of anticancer drugs targeting the apoptosis pathway as a promising new approach to treat cancer. In this study, a co-delivery system of liposomes (arsenic trioxide/curcumin) modified with RGD peptide was designed to aim for enhancing the treatment of prostate cancer cells (PC3 cell line). Liposomal co-loaded curcumin and arsenic trioxide modified by RGD peptide (NLPs-RGD-Cur-ATO) were prepared by thin-layer lipid hydration techniques for the treatment of prostate cancer. The stability of the NLPs-RGD-Cur-ATO was evaluated by particle size analysis through dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). The percentage of cytotoxicity and apoptotic effect in PC3 cells treated with NLPs-RGD-Cur-ATO were detected by MTT and Annexin V-FITC (fluorescein isothiocyanate)/PI affinity assay, respectively. The particle size of NLPs-RGD-Cur-ATO was approximately 100nm, with an encapsulation efficiency of about 99.52% and 70.61%, for ATO and Cur, respectively. Besides, NLPs-RGD-Cur-ATO displayed an enhanced anti-proliferative effect, increased the percentage of apoptotic cells 98 ± 1.85% (p < 0.0001), and significantly reduced EGFR gene expression level (p < 0.001) in the cell line tested. These results indicated that our NLPs-RGD-Cur-ATO co-delivery system was a promising strategy for prostate cancer therapy.