An innovative epinephrine sensor was fabricated by integrating tetrahexahedral (THH) Au-Pd core-shell nanocrystals on reduced graphene oxide (rGO) nanosheets. Furthermore, the nanocomposites combined the large specific areas of rGO with the high-index facets and excellent electrocatalytic activity of the THH Au-Pd nanocrystals, and the nanocomposites were an essential adapter for detecting epinephrine. In the present work, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to identify and characterize these unique nanocomposites, and the results revealed that a unique THH Au-Pd/rGO core-shell nanostructure was synthesized successfully. To further explore the electrochemical behaviors of these nanomaterials at a GC electrode, we applied cyclic voltammetry (CV), differential pulse voltammetry (DPV) and amperometry to study the conductivity and electrocatalytic activity of the proposed sensor, and the results suggested that the sensor based on Au-Pd/rGO presented a lower limit of detection (0.0012 mu M at a signal to noise ratio of 3), wide linear detection range (0.001 mu M to 1000 mu M), and extraordinary selectivity and reproducibility. Moreover, the data showed that the sensor possessed good stability and acceptable accuracy to detect epinephrine in human serum samples. In summary, this work is not only a potential way to manufacture various nonenzymatic sensors but also a significant contribution to further studies in catalysis, cell fuel cells and other relevant applications. (C) 2017 Elsevier Inc. All rights reserved.