Here, a novel biomolecular-repellent electrochemical biosensor platform is fabricated with a hydrophilic material-independent poly-dopamine, Fe3+-mediated tannic acid (TA) deposition and the branched structure of four armed polyethylene glycol (PEG). Dopamine (DA) and TA acted as initiator anchor for surface functionalization. and PEG was then grafted on TA/pDA-coating surface via layer-by-layer (LBL) technique. The whole process of building DNA biosensor platform is optimized and characterized with scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), contact angle measurements (CA). PEG/TA/pDA platform demonstrates excellent characteristics in terms of electrode stability and tendency to resistance to biomacromolecules adsorption. Subsequently, the gold nanoparticles with thiol-modified oligonucleotides were deposited on PEG/TA/pDA platform as enhancer to realize the reliable detection of BACA1 in PBS solution or 10% (V/V) human blood serum. Experimental results shows that charge-transfer resistance (Rct) versus target concentration is constituted from a good linear correlation from 0.1 fM to 10 pM and is associated with a limit of detection as low as 0.05 fM (S/N = 3). Advantageously, this potentially cheap and reusable assay suggests the feasible potential for diagnostic applications in clinical analysis of breast cancer. (C) 2017 Published by Elsevier B.V.