We developed a "signal-on" self-powered biosensing strategy by taking full advantage of both photoelectrochemical biofuel cells (PBFCs) and metal-organic framework (MOF)-controlled release behavior for ultrasensitive microRNA assay. PBFC-based self-powered sensors have the unique characteristics of non-requirement of external power sources, simple fabrication process, miniature size, good anti-interference ability and low cost. Furthermore, based on the target microRNA-induced release of the electron donor ascorbic acid and the high catalytic ability of the biocathode to catalyse the oxygen reduction reaction, photo-driven self-powered biosensors for ultrasensitive microRNA detection were successfully realized. The as-proposed signal-on biosensor not only provides a simple and effective strategy, but also possesses the merits of a wide dynamic concentration response range and high sensitivity for microRNA detection, with a limit of detection down to 0.16 fM.