Electrochemiluminescence (ECL) is one powerful tool in the sensing field, in which the electrochemical workstation is necessary to achieve the electrical/optical signal conversion in the presence of luminescent agents. By contrast, biofuel cells (BFCs) can also provide electricity from renewable biofuels under moderate conditions. More importantly, BFCs with the features of adjustable voltage output and excellent compatibility would well meet the requirement of working voltages for different ECL devices. However, to the best of our knowledge, the BFC-driven luminous system has not been reported. In this work, we constructed, for the first time, a BFC-driven ECL system with fast and stable signal outputs. To demonstrate the proof-of-concept of the BFC-ECL system, the sensitive and selective detection of histidine was achieved, exhibiting great potential among point-of-care diagnoses in remote regions. Overall, this work not only paves a new way for the conversion of chemical energy, electrical energy, and luminous system but also explores the new application of BFC.