Aims: To develop a novel nanomedicine approach for the treatment of multidrug-resistant (MDR) cancer by combining an anticancer drug and suppressors of cellular resistance within one multifunctional nanocarrier-based delivery system (NDS). Materials & methods: The NDS consisted of cationic liposomes (carrier, 100–140 nm), doxorubicin (DOX, anticancer drug), siRNA targeted to MRP1 and BCL2 mRNA (suppressors of pump and nonpump cellular-resistance, respectively). The resulting approximately 500 nm complex has a zeta potential of +4 mV. Results & discussion: The NDS provides an effective co-delivery of DOX and siRNA as well as cell-death induction and suppression of cellular resistance in MDR lung cancer cells. Conclusion: We demonstrate NDS-enhanced efficiency of chemotherapy to a level that cannot be achieved by applying its components separately.