Chalcopyrite bioleaching by 2, 4 and 6 acidophilic strains with the same inoculation density were studied, respectively. The results indicated that the 6-strain community firstly adapted to bioleaching environment, dissolved the chalcopyrite rapidly and maintained an efficient work until late stage. Transcriptome profiles of the 6-strain community at 6th and 30th day during bioleaching process were investigated by RNA-seq. Comparative transcriptomics identified 226 and 737 significantly up-regulated genes at early and late stage, respectively. Gene annotation results revealed that microorganisms adapted to the oligotrophic environment by enhancing cell proliferation, catalytic activation and binding action to maintain their life activities at early stage, and genes related to signal transduction, localization and transporter were highly expressed as an effective response to the stressful late stage. A graphical representation was presented to show how microorganisms adapted and resisted to the extreme environment by their inner functional properties and promoted the bioleaching efficiency.