The present study aims at characterizing the adaptive response of the malaria vector Anopheles gambiae to Fludora Fusion, deltamethrin, clothianidin and transfluthrin. An An. gambiae line carrying resistance alleles to multiple insecticide families at low frequency was created by crossing a multi-resistant strain originating from an intense agricultural area of Côte d’Ivoire and a susceptible strain. The resulting line was then used for selecting, across multiple generations, four lines with Fludora® Fusion, deltamethrin, clothianidin or transfluthrin. At generation G15, a comparative RNA-sequencing approach was used to characterize the impact of selection on each line at the transcriptome scale. Both differential gene transcription levels and selection signatures based on polymorphism data were investigated. Each line was analyzed in quadruplicate, each RNA sample being extracted from 30 three-day-old non-blood fed females. Libraries were sequenced in multiplex as single 75 bp reads on a NextSeq 500 sequencer (Illumina).