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Cytochrome P450 monooxygenase (P450)-mediated detoxification is an important mechanism involved in the resistance to neurotoxic pesticides. However, the molecular basis of the mechanism of P450s, as associated with the resistance to growth regulator insecticides (IGRs) remains largely unknown. In this study, a resistance strain (YN-BPF) of Laodelphax striatellus was developed, with 59.9-fold resistance to buprofezin, through 42 generations of discontinuous selections of the susceptible strain (YN) with buprofezin (an IGR). A synergistic study in vivo and a biochemical study in vitro indicated that an enhanced detoxification mediated by P450s to some extent contributes to the buprofezin resistance in the YN-BPF strain. A total of 38 cDNA sequences encoding tentative unique P450 genes were identified in an L. striatellus transcriptome database, and the mRNA expression level of these genes was examined in the YN and YN-BPF strains using quantitative real-time PCR (qPCR). A single P450 gene, CYP6CW1, was highly overexpressed (22.78-fold) in the YN-BPF strain compared with the YN strain. Based on the analysis of insects with similar genetic backgrounds, our results provided evidence for the role of CYP6CW1 in the resistance of L. striatellus to buprofezin.