In this study, we dissected the molecular basis of a monooxygenase-mediated resistance to pyrethroid in one of the major African malaria vectors An. funestus demonstrating that (i) allelic variation in cytochrome P450 genes is a key molecular mechanism conferring pyrethroid resistance in field mosquitoes, and (ii) detecting key amino acid changes in resistant P450 alleles responsible for pyrethroids-metabolising efficiency. Here, CYP2B6 is linked to malaria.