Insecticide resistance has led to the failure of chemical pest control and threatens global food security, with transcriptional regulation of detoxification genes by xenobiotic-response transcription factors (TFs) playing a key role. However, the regulation mechanism remains unclear in most crop insect pests. This study characterized the role of the nuclear receptor NlNR2E in response to insecticides in the brown planthopper Nilaparvata lugens, a destructive rice pest. Using DAP-seq, we identified detoxification gene promoters targeted by NlNR2E. NlABCG23, encoding an ATP-binding cassette (ABC) transporter, showed significantly reduced expression after the RNA interference (RNAi) knockdown of NlNR2E. Dual-luciferase reporter, yeast one-hybrid, and electrophoretic mobility shift assays confirmed that NlNR2E directly binds to NlABCG23 promoter, thus activating NlABCG23 expression. RNAi knockdown of NlABCG23 significantly reduced resistance to imidacloprid, dinotefuran, pymetrozine, and chlorpyrifos in N. lugens. These findings illustrated how xenobiotic-induced TF regulates the ABC transporter, conferring resistance to multiple insecticides in planthoppers.