Nickel-substituted layered perovskite PrBaCo2 − x Ni x O5 + δ (PBCN) powders with various proportions of nickel (x = 0, 0.1, 0.2, and 0.3, abbreviated as PBCN-0, PBCN-1, PBCN-2, and PBCN-3, respectively) are investigated as potential cathode materials for intermediate temperature solid oxide fuel cells (IT-SOFCs) based on the yttria-stabilized zirconia (YSZ) electrolyte. It is found that PBCN-1 has the highest electrical conductivity of 1,397 S cm−1 at 400 °C. Substitution of Co by Ni decreases the thermal expansion coefficient (TEC) clearly. The average TEC at the temperature range of 35–900 °C decreases from 22.8 × 10−6 K−1 for PBCN-0 to 18.9 × 10−6 K−1 for PBCN-3. The polarization resistances of PBCN samples on YSZ electrolyte at 800 °C are 0.053, 0.048, 0.052, and 0.042 Ω cm2 for PBCN-0, PBCN-1, PBCN-2, and PBCN-3, respectively. The single fuel cell with the configuration of PBCN-3/YSZ/Pt delivers the highest power densities of 100, 185, 360, 495, and 660 mW cm−2 at 600, 650, 700, 750, and 800 °C, respectively.