This work proposes the concept of single‐cell microRNA (miR) therapy and proof‐of‐concept by engineering a nanopipette for high‐precision miR‐21‐targeted therapy in a single HeLa cell with sensitive photoelectrochemical (PEC) feedback. Targeting the representative oncogenic miR‐21, the as‐functionalized nanopipette permits direct intracellular drug administration with precisely controllable dosages, and the corresponding therapeutic effects can be sensitively transduced by a PEC sensing interface that selectively responds to the indicator level of cytosolic caspase‐3. The experimental results reveal that injection of ca. 4.4 × 10−20 mol miR‐21 inhibitor, i.e., 26488 copies, can cause the obvious therapeutic action in the targeted cell. This work features a solution to obtain the accurate knowledge of how a certain miR‐drug with specific dosages treats the cells and thus provides an insight into futuristic high‐precision clinical miR therapy using personalized medicine, provided that the prerequisite single‐cell experiments are courses of personalized customization. The concept of high‐precision single‐cell microRNA therapy is proposed and devised by a functional nanopipette, which allows precise miR‐21 inhibitor delivery to induce cell apoptosis and responds selectively to caspase‐3 of a sensitive photoelectrochemical feedback. It can reveal what the precise drug amount can cause the effective therapeutic action.