The challenge of detection of sialic acids (SA) on cell surfaces is due to its high activity and short half-life time. Here, based on an amicable platform of three-dimensional (3D) zinc oxide (ZnO) nano-biointerfaces which is known to promote cell adhesion, a new electrochemical cytosensor was reported. The 3D ZnO pillars were fabricated by one-step hydrothermal method, and then decorated with Sambucus nigra agglutinin (SNA) after ammoniation, which was used to identify SA that comes from cells adhering to the 3D nano-interfaces. The construction and properties of 3D nano-interfaces and electrochemical cytosensor were characterized scanning electron microscopy (SEM), energy disperse spectroscopy (EDS), elemental mapping, fourier transform infrared (FTIR) spectra, water contact angle, microscope, fluorescence microscope, MTT test and laser confocal microscope. Further, the electrochemical performances of this cytosensor we proposed were investigated. Results indicated that the asobtained 3D ZnO nano-interfaces showed good cells adhesion, and the cytosensor exhibited high electroactivity and good reproducibility with a lower detection limit (13 cell mL(-1)) and a wide linear range (1.0 +/- 101 to 1.0 +/- 107 cells mL(-1)). The design strategy may provide new insights of 3D micro/nano-biointerfaces, which can guide cell fate and be beneficial to early monitoring of tumor cells. (C) 2018 Elsevier Ltd. All rights reserved.