Membrane protein, a novel surface biomarker, plays an important role in cell recognition and disease diagnosis. Accurate recognition of membrane protein ensure high specificity of cell identification, while introducing signal molecules onto cell membrane is critical to achieve high sensitivity. In this work, we introduced a simple and universal signal labeling approach for cancer cell detection based on mild reduction-mediated cell engineering. This approach included the mild reduction of disulfide bonds within membrane proteins and the introduction of DNA bridge complex-templated silver nanoclusters (DNA bridge-AgNCs) through the thiol-maleimide conjugation. The mild reduction reactions on the cell surface significantly increased the binding sites for signal labeling, and DNA bridge-AgNCs served as a scaffold of signal amplification, resulting in a wide linear range from 50-2 × 10 cells, and a detection limit of 15 cells. In addition, the method also showed good selectivity in complex environment. Therefore, this method may have great application space in the field of cell detection and even disease diagnosis in the near future.