Herein, we demonstrate a high-accuracy H2O2 selective organic-inorganic 3D-heterointerface based on catalyt-ically in-situ reduced Prussian-blue nanoparticles (PBNPs), Poly (3,4-ethylene dioxythiophene):poly (styrene sulfonic acid) (PEDOT:PSS) and water-soluble Silkworm protein (SWp). PBNPs were immobilized on an indium tin oxide-coated glass (ITO) electrode through the electrochemical polymerization process of PEDOT:PSS and the yielding intertwining composite was templated by the use of SWp, simultaneously. Since PSS and SWp act as poly-anionic and poly-cationic charge compensating elements, the sensing system's potential cycling and amperometric response stability have been significantly enhanced thanks to the arising physical blockage effect. Constructed sensing system showed a substantially high sensitivity (1031.7 mu A mM-1 cm-2) and a low limit of detection value (LOD, 0.29 mu M) between 1 and 130 mu M H2O2. Eliminating the possible signal disruptions by common anion and cations in tap water, the (PEDOT:PSS:PB):SWp interface successfully selected H2O2 between the concentration of 10-40 mu M with high recovery and relatively low RSDs oscillating between 94.2-110.9% and 2.9-5.1%, respectively. It is thought that the proposed heterointerface can be used in the field of sensor, biosensor and fuel cell systems run by H2O2 assay based on 3D scaffold-templated conductive polymer-PBNPs network.