In this work, a sensitive electrochemical DNA sensor based on avidin modified electrode and DNA-functionalized Cds nanoparticle (DFNP) was developed. The DNA-Functionalized Cds nanoparticle contained two kinds of DNA, one was hairpin probe DNA with a biotin at the 3’’ terminal and a thiol at the 5’ terminal, the other is linearity signal DNA. Without hybridized with target DNA, the loop of hairpin impeded biotin linked with avidin on electrode. However, after target hybridization, hairpin was opened and biotin was recognized by avidin resulting in DNA-functionalized Cds nanoparticle was brought on electrode surface. Electrochemical signals of methylene blue (MB) bound to the signal DNA were measured by differential pulse voltammetry (DPV). Introduction By using this new method, we demonstrate that this prototype sensor has been able to detect as low as picomolar p53 tumor suppressor gene with excellent differentiation ability for even single mismatches.