Developing efficient platinum-based electrocatalysts with super durability for the oxygen reduction reaction (ORR) is highly desirable to promote the large-scale commercialization of fuel cells. Although progress has been made in this aspect, the electrochemical kinetics and stability of platinum-based catalysts are still far from the requirements of the practical applications. Herein, PtPdFeCoNi high-entropy alloy (HEA) nanoparticles were demonstrated via a high-temperature injection method. PtPdFeCoNi HEA nanocatalyst exhibits outstanding catalytic activity and stability towards ORR due to the high entropy, lattice distortion, and sluggish diffusion effects of HEA, and the HEA nanoparticles delivered a mass activity of 1.23 A/mg_Pt and a specific activity of 1.80 mA/cm_Pt², which enhanced by 6.2 and 4.9 times, respectively, compared with the values of the commercial Pt/C catalyst. More importantly, the high durability of PtPdFeCoNi HEA/C was evidenced by only 6 mV negative-shifted half-wave potential after 50,000 cycles of accelerated durability test (ADT).