AbstractSitobion avenae presents a major challenge, leading to significant reductions in wheat yield per year. This study aimed to explore the potential of targeting Voltage-gated Sodium Channels (VGSCs) in S. avenae through RNA interference as a means to combat this pest. Two-dimensional polyacrylamide gel electrophoresis was conducted to identify RNAi targets in S. avenae. VGSCs were amplified by reverse transcriptase PCR, sequenced, and deposited in Gen Bank. The ID allotted was OR777606. ERNAi was utilized to generate 143 small interfering RNA (siRNA) sequences and one double-stranded RNA target. Phylogenetic analysis revealed evolutionary links between the VGSCs gene in grain aphids and related aphid species like peach, potato, pea, and Russian wheat aphids. VGSCs are essential transmembrane proteins crucial for nerve cell action potentials and are common targets in commercial insecticides. While RNAi has traditionally been employed in functional genomics, it is increasingly recognized as a promising tool for agricultural pest control. Quantitative real-time PCR analysis revealed aphid mortality, decreased fecundity, and shortened lifespan; attributable to the down-regulation of VGSCs gene expression (35%), and mortality up to 61% among 3rd instar nymphs. Additionally, adult aphids exposed to dsVGSCs during their nymph stage exhibited reduced reproductive capacity and longevity. The findings suggest VGSCs as a promising RNAi target; having potential applications in agricultural pest management.