To seek a sustainable way of CO2 sequestration and conversion, enzymatic electrosynthesis (EES) of formate from CO2 reduction has been investigated in a hybrid biofuel cell system. In an enzymatic fuel cell (EFC), waste CO2 species are specifically reduced to energy-rich product of formate under mild biological conditions. Efficient formate production can be achieved at lowered electrode potential owing to the electrochemically active participation of formate dehydrogenase (CbFDH) as a biocatalyst. Electropolymerized neutral red (PolyNR) is proven to be a promising modifier to enhance the electrochemical behavior of enzymatic electrode, as well as a reducing reagent to regenerate mediator of NADH in enzymatic CO2 reduction. Electrons for EES are extracted from the organic pollutants in wastewater by microbial fuel cell (MFC) stacks arranged in series and/or parallel with different unit numbers (n = 1, 2 and 3). The maximum formate production rate reaches around 60 mg L-1 h(-1) with a Faraday efficiency of 70% in the EFC powered by a three-MFC stacked in series. In view of practical applications, the hybrid MFC-EFC system has been demonstrated to be advantageous in both product specificity and energy sustainability. (C) 2017 Elsevier Ltd. All rights reserved.