Small interfering RNAs (siRNAs) - have a huge potential in treatment of many diseases resulting from aberrant gene expression including cancer, diabetes and atherosclerosis. In order to realize the therapeutic potential of siRNAs, the most important hurdle i.e. crossing cell membrane and delivery to cytoplasm in a stable form, must be addressed by developing effective and safer delivery platforms. In the present study, we have taken a systematic approach to investigate the use of gold nanoparticles as delivery platforms for firefly siRNAs and the effect of chemical modifications: oligo ethylene glycol (OEG) and lipofectamine on gold nanoparticle-siRNA conjugates. Thiolated siRNAs were covalently conjugated to gold nanoparticles (20 nm) and these conjugates (GNP-siRNA) were either used alone, or further modified with OEG (GNP-siRNA-OEG) or lipofectamine (GNP-siRNA-lipofectamine) followed by incubation with 3T3-L1 cells expressing the firefly luciferase gene (FFL). The analyses revealed that FFL siRNAs transfected with lipofectamine or GNP-siRNA-OEG or GNP-siRNA-lipofectamine have shown knockdown. However, there was no knockdown with AuNP-siRNA. These results suggest that OEG has beneficial properties on AuNP-siRNA conjugates either affecting cell uptake or routing the conjugates to the cytoplasm or both and thus improving delivery of siRNAs to the cytoplasm in the effective knockdown of the FFL gene.