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Abstract To overcome the drug resistance in MCF7 cancer cells and enhance their sensitivity to cisplatin, a liposomal (Lip) nanocarrier modified by arginine-glycine-aspartic acid (RGD) to co-deliver cisplatin (Cis) and miRNA biomolecule (miR-34a) was investigated. The efficiency of this nanocarrier was evaluated through in vitro and in vivo assays against MCF7 and 4T1 cells, respectively. The in vitro results demonstrated that the miR34a-Cis-Lip-RGD formulation had significantly higher efficiency and also a higher apoptotic effect compared to both miR34a-Cis and miR34a-Cis-Lip (76.24%, 58.29%, and 56.2%, respectively). Additionally, miR34a-Cis-Lip exhibited an overall CI value below 1, indicating a synergistic effect of Cis and miR-34a within the Lip system. The miR34a-Cis-Lip-RGD increased the Bax gene expressions compared to both miR34a-Cis-Lip and Cis-miR34a, possibly due to the integrin receptors on the cells, leading to higher uptake. The efficiency of miR34a-Cis-Lip-RGD in reducing tumor size was significantly higher than Cis-miR34a and miR34a-Cis-Lip. The lower volume of the tumor in the group treated with Cis-miR34a-Lip-RGD is presumed to be attributed to improved cellular uptake facilitated by the RGD modification, which enhances the targeted delivery of the therapeutic payload to cancer cells. The overall weight of the mice in all the groups did not exhibit significant changes. This consistent weight maintenance implies the safety of the designed delivery system for vital organs, indicating that the designed delivery system may offer a promising solution to minimize unwanted side effects associated with conventional cancer treatments.