Pediatric head and neck cancers account for overall 12% of all pediatric cancers. Despite recent advances in therapeutic modalities, children with tumor metastasis have poor prognosis. Therefore, there is an unmet need for new and effective treatment modalities for pediatric head and neck cancers. The present study describes a simple and efficient method for fabrication of cationic lipid‑polymer hybrid nanoparticles (CLPNs) for co‑delivery of cisplatin (CDDP) and DNA (CDDP/DNA CLPNs) for the therapy of childhood head and neck cancers. CDDP/DNA CLPNs were prepared by the modified double emulsion solvent evaporation method with self‑assembly. CDDP‑loaded CLPNs (CDDP CLPNs), CDDP-loaded polymeric nanoparticles (PNPs) (CDDP PNPs), and DNA‑loaded Lipofectamine® 2000 (DNA LIPO) were also prepared for comparison. The results illustrated that the concentration of the cationic lipid has influence on the characteristics of CLPNs. In vitro anticancer effect, in vitro transfection efficiency, in vivo antitumor and gene delivery efficacy of CDDP/DNA CLPNs have advantages over other formulations tested. In conclusion, outstanding delivery ability of CLPNs for both CDDP and DNA could combine the therapeutic efficiency of both drug and gene for the treatment of pediatric rhabdomyosarcoma (RMS).