High-entropy layered double hydroxides (HE-LDHs) are emerging as promising electrocatalysts towards the OER due to their high-entropy effect and the cocktail effect. However, the catalytic activity and stability of HE-LDHs is, as yet, unsatisfactory. Herein, we designed FeCoNiCuZn LDHs with rich cation vacancies, which need only low overpotentials of 227, 275 and 293 mV to reach 10, 100 and 200 mA cm-2, respectively, and show almost no decay up to 200 h at 200 mA cm-2. DFT calculations validate that the cation vacancies can boost the intrinsic activity of HE-LDHs through optimizing the adsorption energy of OER intermediates.