During high-temperature operation of a solid oxide fuel cell, the stresses caused by mismatch of thermal expansion coefficients between different materials and external mechanical loads may cause the rising of damage risk of nickel-yttria-stabilized zirconia anode. It is quite difficult to quantify the mechanical characteristics of a composite anode without investigating on the stress distribution in its real microstructure. However, the high operating temperature and extremely complex microstructure in micro-scale determine the high difficulty in in-situ measurement of thermo-mechanical stress distribution. In this work, the microstructures of six different anode samples, fabricated by using identical nickel oxide-yttria-stabilized zirconia powder mixture, are reconstructed in three-dimension based on the dual-beam focused-ion-beam-scanning-electron-microscopy. The three-dimensional thermo-mechanical stress distributions of different microstructures are conducted at operating temperature based on the finite element method. The effects of both thermal expansion coefficients mismatch between nickel and yttria-stabilized zirconia and external mechanical loads are analyzed. The mechanical failure probabilities of yttria-stabilized zirconia phase in different reconstructions are estimated based on the obtained stress distributions to investigate the influence of microstructure characterizations on nickel-yttria-stabilized zirconia anode strength. (C) 2020 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.