We report a nanowire-based biofuel cell based on a single proton conductive polymer nanowire for converting chemical energy from biofluids, such as glucose/blood, into electricity, with glucose oxidase and laccase as catalyst. The glucose is supplied from the biofluid, the nanowire serves as the proton conductor, and the whole cell can be realized at the nano/micrometer scale. The biofuel cell composed of a single nanowire generates an output power as high as 0.5-3 mu W, and it has been integrated with a set of nanowire-based sensors for performing self-powered sensing. This study shows the feasibility of building self-powered nanodevices for the biological sciences, environmental monitoring, defense technology, and even personal electronics.