Abnormal expression of hydrogen peroxide (H₂O₂) indicates the disorder of cell functions and is able to induce the occurrence and deterioration of numerous diseases. However, limited by its low concentration under pathophysiological conditions, intracellular H₂O₂ is still difficult to be determined to date. Herein, to achieve sensitive quantification of H₂O₂ in cells, CIS/ZnS/ZnS quantum dots (CIS/d-ZnS QDs) are retrofitted with ZnO shells via self-passivation. Different from the traditional self-passivation of QDs, self-passivation of CIS/d-ZnS QDs is realized facilely without the assistance of additional cation ions, which improves optical properties of QDs and equips the QDs with a sensing layer. As a result, the CIS/d-ZnS/ZnO QDs exhibit enhanced fluorescence emission and stability. Relying on the decomposition of ZnO and ZnS shells in the presence of H₂O₂, aggregated QDs reveal exciton energy transfer effect, resulting in fluorescence quenching. On a basis of this principle, a fluorescence H₂O₂ sensor is further established with the CIS/d-ZnS/ZnO QDs. To be noted, since the equipped ZnO shells are more susceptible to H₂O₂ than original ZnS shells, analytical performance of the fluorescence sensor is remarkably promoted by the self-passivation of QDs. Accordingly, H₂O₂ can be measured in 5 orders of magnitude with a limit of detection (LOD) of 0.46 nM. Furthermore, because the ZnO shells improve H₂O₂-responsive selectivity and sensitivity, variation of H₂O₂ in cells can also be quantified with the CIS/d-ZnS/ZnO QDs. In this work, sensitive detection of intracellular H₂O₂ is enabled by equipping QDs with a sensing layer, which provides an alternative perspective of functionalizing nanomaterials for analytical applications.