In this study, we aimed to develop a novel positive charged nucleic acid delivery system for the treatment of glioblastoma. For this purpose, Epidermal Growth Factor Receptor (EGFR) which plays a prominent role in glioblastoma was selected as a target. Cationic solid lipid nanoparticles (cSLN) were developed by microemulsion dilution method using cetyl palmitate as matrix lipid, Cremephor RH40 and Peceol as surfactants, and ethanol as cosurfactant. Characterization studies showed that obtained nanoparticles are positively charged and has an appropriate particle size for nucleic acid delivery (<20 nm). Gel retardation assay revealed that cSLNs have complexation ability with siRNA EGFR (cSLN:siRNAEGFR) and this complex is able to protect siRNA from serum- mediated degradation up to 6 h. The cytotoxicity evaluation of nanoparticles performed on U87 Human Glioblastoma Cell Line. Furthermore, in vitro delivery of siRNA-EGFR via cSLN inhibited EGFR expression significantly at 50nM siRNA dose compared to free siRNA-EGFR at the same dose on U87 cell line (p<0.05). Based on these findings, we propose that the developed cSLN system may has a potential as a siRNA delivery system for glioblastoma.