In this work, an efficient dual-protein (lipase and hemoglobin) system was successfully constructed for the regioselective synthesis of quinoxalines in water. A set of quinoxalines were obtained in high yields under optimal reaction conditions. This dual-protein method exhibited a regioselectivity higher than those of previously reported methods. This study not only provides a green and mild strategy for the synthesis of quinoxalines but also expands the application of lipase and hemoglobin in organic synthesis.