Production of renewable hydrogen energy by water electrolysis is an effective method to reduce carbon emissions. In comparison to freshwater, seawater is a more suitable raw material for electrolysis thanks to its abundant reserves. However, the reported catalysts are not suitable for large-scale commercial application as a result of the reduction of catalyst stability and activity within complex natural seawater. To better promote the rational design of electrocatalysts and tackle the challenges of seawater splitting, this mini review summarized recent advances in rational design electrocatalysts for seawater splitting, including constructing a hierarchical structure, decorating a corrosion resistance layer, and introducing a charge redistribution within the system. Afterward, a perspective in the development of large-scale seawater electrolysis for hydrogen production is also proposed.