Deltamethrin is a widely used type-II pyrethroid insecticide in agricultural, industrial and domestic pest control. Previous studies have shown that deltamethrin can induce ER stress response in vivo. However, it is still unclear whether deltamethrin can disturb protein homeostasis. To investigate how deltamethrin affects ER protein homeostasis, we used a C. elegans model of protein misfolding. In the current study, deltamethrin induced ER stress response in C. elegans. Moreover, exposure to deltamethrin increased the accumulation of unfolded and misfolded proteins in a C. elegans model of polyglutamine aggregation in body wall muscles. Deltamethrin also increased the toxicity of polyglutamine aggregates in C. elegans, as characterized by decreased locomotion with deltamethrin treatment. These data indicate that exposure to deltamethrin can induce ER stress response, increase the accumulation and proteotoxicity of unfolded and misfolded proteins. As ER stress plays a pathological role in many diseases, these findings provide evidence for the potential pathological role of deltamethrin in ER stress-related diseases.