Solid oxide fuel cell (SOFC) is expected to be a crucial technology in future power generation due to its advantages of high efficiency, fuel adaptability, all-solid state, modular assembly, and low pollution. The Ni/YSZ (yttrium-stabilized zirconia) cermet is the most popular anode material in SOFCs. However, a major problem is that it can be easily oxidized, thus resulting in the decline of long-term stability and activity as an anode catalyst. A better performance of the Ni/YSZ cermet can be obtained by improving its microstructure as well as the Ni distribution in it. Interactions between Ni and the yttria-stabilized zirconia (YSZ) (111) or oxygen-enriched YSZ(111) (YSZ+O) surface are studied in terms of the first-principles method based on the density functional theory with particular focus put on the activity of the Ni atom at the interface. The geometric and electronic structures of CO and O2 on the Ni1 (the single Ni atom)/YSZ and Ni1/YSZ+O surfaces are also studied. It is found that the Ni atom tends to be adsorbed to O sites and away from the Y atoms on both the surfaces. The most favorable adsorption site is the oxygen vacancy, which has an adsorption energy of 2.85 eV. Compared with YSZ, the single Ni atom loses 1.06 electrons and is oxidized as Ni+ on YSZ+O, which produces a strong interaction between the Ni atom and YSZ+O. Strong adsorption is mainly attributed to the interaction between Ni 3d and Ou 2p orbitals. And the oxidation of Ni can lead to the decrease of electrocatalytic activity of the Ni catalyst. The d-band DOS (density of states) peaks of the Ni1/YSZ+O are lower than that of the Ni1/YSZ, and the corresponding d-band centers are shifted away from the Fermi level to lower energy with the d value of -3.69 eV; therefore the CO and O2 adsorption is weakened. While the adsorption energy for CO on the Ni1/YSZ+O (0.42 eV) is much lower than that on the Ni1/YSZ surface (1.78 eV). In addition, the adsorbed CO gains 0.07 electrons, less than those on the Ni1/YSZ surface (0.34 e). The adsorption energy of O2 on Ni1/YSZ+O also decreases (0.34 eV) and gains fewer electrons (0.24 e) as compared with the corresponding values (2.57 eV, 1.15 eV) on Ni1/YSZ. Results would improve our understanding on the mechanism of oxidation of Ni on the Ni/YSZ anode of SOFCs and would be of great importance for designing highly active catalysts used for fuel cells.