Face-centered cubic (FCC) high-entropy alloys (HEAs) have good mechanical properties, but their low hardness makes it difficult to meet the wear resistance required by actual working conditions. Therefore, the effect of ion nitriding on the microstructure, mechanical properties and tribological properties of Fe40Mn20Cr20Ni20 FCC HEA was investigated in this work. It was found that the activation energy of ionic nitriding of Fe40Mn20Cr20Ni20 FCC HEA was 41.388 kJ/mol, which was lower than that of CoCrFeMnNi HEA (64.034 kJ/mol). When nitriding at 400 °C, the nitrided layer was mainly expanded FCC phase; above 400 °C, the expanded FCC phase began to decompose into CrN and γ phase, the generation of γ phase and the growth of CrN caused the hardness of the nitrided layer to decrease with the increase of temperature. After evaluating the hardness, brittleness and nitriding growth kinetics of the nitrided layer obtained from different nitriding processes, the nitrided layer obtained from the nitriding process with the nitriding temperature of 550 °C and the nitriding time of 5 h was selected for the friction and wear test under different normal forces and temperatures. It was demonstrated that at 20–400 °C, the wear resistance of the nitrided alloy was relatively stable over a wide range of normal forces and was substantially improved over the matrix alloy. At 500–600 °C, due to a certain degree of softening of the surface of the nitrided layer, the wear rate increased slightly, but it was still much lower than that of the matrix alloy.