In this work, we report a multiplexed electrochemical DNA sensor for highly specific single-nucleotide polymorphism (SNP) detection by using oligonucleotide-incorporated nonfouling surfaces (ONS). A typical "sandwich" scheme was employed to perform the SNP assay. The presence of the target DNA templated the ligation between the capture probe DNA anchored on gold electrodes and the tandem reporter probe tagged with a biotin moiety, which could be transduced to peroxidase-based catalyzed amperometric signals. This method could effectively differentiate SNP sites with only one-base mismatch. Importantly, the differentiation ratio was significantly higher than that with surfaces without the nonfouling property, which clearly demonstrated the superiority of the ONS strategy.