In our previous research, we identified that treatment of Helicoverpa armigera with ZQ-8 led to upregulation of CYP450 genes. To clarify the metabolic pathway of ZQ-8, this study analyzed the expression of CYP450 genes and proteins in H. armigera after ZQ-8 treatment through transcriptomics and proteomics. Molecular docking, recombinant protein expression, and surface plasmon resonance techniques were employed to investigate the interactions between ZQ-8 and P450 proteins. The oxidative reduction related pathways were significantly enriched in H. armigera larvae treated with ZQ-8, with an increase in the expression of CYP6B2 and CYP6B6 genes. The CYP6B2 and CYP6B6 proteins exhibited significant expression following ZQ-8 treatment. ZQ-8 demonstrated rapid binding and stable dissociation characteristics with CYP6B6, characterized by a dissociation constant (K