This study investigated the direct microbial reduction of perchlorate using domesticated activated sludge and showed the interaction effect of water quality factors on perchlorate bio-reduction. The dominant perchlorate-reducing bacteria belong to Dechloromonas sp., which was successfully acclimated from regular activated sludge after 20 days domestication. Batch reduction experiments indicated that high bio-reduction efficiency of perchlorate could be achieved at 303-313 K and pH = 6.5-7.5. Perchlorate-reducing bacteria can more efficiently utilize acetate and butanedioic to reduce perchlorate compared with the other electron donors that significantly affect the microbial community structure and dominant bacteria of activated sludge. The three-level and three-variable Box-Behnken Design response surface method predicted a maximum perchlorate reduction efficiency of 100% under the following optimal conditions: pH= 7.5, 308 K, and 0.51 mg/L of acetate. Furthermore, the influence of two factors on per chlorate reduction was in this order: interaction between pH and acetate > interaction between pH and temperature > interaction between temperature and acetate. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.