Hydrogen production via electrochemical splitting of seawater is highly desirable but still facing great challenges. Herein, we report the facile preparation of medium-entropy oxyhydroxides on Ni(OH)2 nanosheets via surface reconstruction and entropy engineering strategies, achieving enhanced electrocatalytic activity and stability for oxygen evolution reaction (OER) in alkaline seawater. The electrochemical oxidation is conducted on Ni(OH)2 nanosheets to create abundant reactive oxygen (reactive-O) atoms on the reconstructed surface, thus forming a reactive-O enriched surface on Ni(OH)2 (NiOx/Ni(OH)2). Additionally, cations are incorporated onto the reconstructed surface of NiOx/Ni(OH)2 via an electrodeposition method, forming the medium-entropy oxyhydroxides on Ni(OH)2 nanosheets ((FeCoCrNi)Ox/Ni(OH)2). Benefiting from the composition and structure advantages, the resulting (FeCoCrNi)Ox/Ni(OH)2@NF demonstrates obviously enhanced performances for OER electrocatalysis, with an overpotential of 239 mV at the current density of 10 mA cm−2 and a low Tafel slope of 24.66 mV dec−1 in 1.0 M KOH + 0.5 M NaCl solution. Furthermore, it exhibits exceptional durability for OER electrocatalysis in alkaline seawater, maintaining over 90.7 % of the OER current density after 100 h.