Polyoxometalates (POMs) as efficient electrochemical catalytic components were successfully loaded on three-dimensional graphene foam (3DGF) forming novel POM-based carbon-material of POM@3DGF. Being the first time, POMs were loaded onto 3DGF matrix as a highly selective electrochemical biosensor, by which xanthine (Xan) and guanine (Gua) can be detected simultaneously with separated electrochemical signals. At pH = 2.0 buffer solution, two oxidation signals ascribed to Xan and Gua bases were observed at about 1.05 and 1.13 V respectively, which could not be observed separately by previous reported 1D carbon nanotube or 2D graphene modified GCEs. Furthermore, POM@3DGF modified GCE can be used to detect Xan and Gua bases in MCF-7 cell lysates, which extends the detection species of purines in cells by electrochemical approach. Our study opens a new avenue to accurate electrochemical assay of cellular purines by POMs-based carbon-materials. (C) 2015 Elsevier Ltd. All rights reserved.