Abstract: A simple and low- cost method for the determination of protein was established. This method was based on the terminal protection of small-molecule-linked DNA and used the DNAstabilized Ag nanoclusters（DNA-Ag NC）. This sensor could detect the target protein streptavidin （SA）as low as 7. 92 ng/mL with a linear range from 10 to 1 000 ng/mL and exhibited good selectivity. Besides，this method could be used as a universal method for protein and cell determination by changing the corresponding small molecule. More importantly，the introduction of Exonuclease I（Exo I）hydrolyze probe DNA that didn′t bind to a target protein into mononucleotides，thus the DNA-Ag NC could not be formed，the background interference was reduced and the sensitivity was improved. Furthermore， the probe did not need to modify fluorescent dyes， and the raw materials for synthesizing silver clusters were cheap and easy to obtain，which greatly saved the cost.

Key words: Ag nanoclusters, terminal protection of small-molecule-linked DNA, enzymolysis, biosensor, streptavidin