High catalytic activity, low-cost and stable cathode in a temperature range 550–700 °C is essential for the development of protonic ceramic fuel cells (PCFCs). Doping nickel into perovskite La0.5Sr0.5MnO3-δ(LSM) is designed as a cobalt-free cathode based on theoretical calculations and experiments. La0.5Sr0.5Mn0.9Ni0.1O3-δ (LSMNi) as cathode shows higher proton conductivity and ORR activity than the undoped LSM. The PCFCs with LSMNi exhibit low polarization resistance and high peak power density 1.1 W cm−2 at 700 °C. The density functional theory simulations indicate that doping with nickel decreases the oxygen vacancy formation energy and promotes the formation of hydroxide defects. The decrease in proton transfer energy barriers and hydration energy improves the proton conductivity. The improved performance is attributed to fast proton transfer and rapid kinetics of oxygen reduction on the surface of LSMNi. This work provides a novel approach to design cobalt-free cathode for a protonic ceramic fuel cell.