A voltage-gated sodium channel (VGSC) plays a crucial role in insect electrical signals, and it is a target for various naturally occurring and synthesized neurotoxins, including pyrethroids and dichlorodiphenyltrichloroethane. The type of agent is typically widely used to prevent and control sanitary and agricultural pests. The perennial use of insecticides has caused mutations in VGSCs that have given rise to resistance in most insects. These mutations are located among the two pyrethroid receptors, i.e., PyR1 and PyR2, as predicted by previous studies. The two binding regions are relatively symmetrical, and here we focus on the linkers between S4 and S5 of Domains I and II. The S4-S5 linker can promote a rapid increase in sodium current and the onset of action potential. By predicting mutations in 19 other amino acids at all the amino acids on S4-S5 linkers, their harmfulness is analyzed, and whether they affect protein stability and drug binding is determined. Through molecular docking and based on docking scores, four mutations were predicted to affect the binding of sodium channels to pyrethroids. Mutations G255V, G255A, A906V, and A906T were introduced into the VGSC of Blattella germanica (BgNa