Seawater electrolysis not only affords a promising approach to produce clean hydrogen fuel but also alleviates the bottleneck of freshwater feeds. Here, a novel strategy for large-scale preparing spinel Ni x Mn 3-x O 4 solid solution immobilized with iridium single-atoms (Ir-SAs) is developed by the sol-gel method. Benefitting from the surface-exposed Ir-SAs, Ir 1 /Ni 1.6 Mn 1.4 O 4 reveals boosted oxygen evolution reaction (OER) performance, achieving overpotentials of 330 and 350 mV at current densities of 100 and 200 mA cm -2 in alkaline seawater. Moreover, only a cell voltage of 1.50 V is required to reach 500 mA cm -2 with assembled Ir 1 /Ni 1.6 Mn 1.4 O 4 ‖Pt/C electrode pair under the industrial operating condition. The experimental characterizations and theoretical calculations highlight the effect of Ir-SAs on improving the intrinsic OER activity and facilitating surface charge transfer kinetics, and evidence the energetically stabilized *OOH and the destabilized chloride ion adsorption in Ir 1 /Ni 1.6 Mn 1.4 O 4 . This work demonstrates an effective method to produce efficient alkaline seawater electrocatalyst massively.