Abstract: High-pressure hydrogen production via water electrolysis holds significant promise for enhancing hydrogen storage, transportation, and utilization processes, potentially reducing overall hydrogen costs. Proton exchange membrane (PEM) water electrolysis has been widely adopted for high-pressure hydrogen production, demonstrating advantages in energy consumption and capital cost reduction. However, under high-pressure conditions, PEM electrolysis cell face the challenge of significant hydrogen crossover. The increased hydrogen crossover rate leads to efficiency losses in hydrogen production and, more critically, raises the hydrogen-in-oxygen concentration, which could surpass the explosion limit. This review presents the current progress in high-pressure hydrogen production through PEM water electrolysis, summarizing the development of high-pressure PEM electrolysis cell and corresponding hydrogen production systems. The primary factor contributing to the loss of hydrogen production efficiency is hydrogen crossover through the PEM. The hydrogen crossover rate has been observed to increase linearly with the current density in PEM electrolysis cell. Two mechanisms—the pressure-enhancement model and the supersaturation model—have been proposed to explain the relationship between the hydrogen crossover rate and the current density. Several strategies, such as modifying the proton exchange membrane and adding hydrogen elimination catalysts at the anode, have been suggested to mitigate the increase in hydrogen-in-oxygen content caused by the hydrogen crossover. Additionally, the recently developed decoupled water electrolysis (DWE) technology, which uses redox mediators to temporally or spatially separate the hydrogen and oxygen evolution reactions, offers a potential solution to the hydrogen crossover issue. This review further examines the principles and technical characteristics of various DWE systems. Depending on the type of mediator, DWE systems can be classified into solid-phase mediator and liquid-phase mediator systems. Solid-phase mediators, such as Ni(OH)2 and MnO2, are typically derived from battery electrode materials, while liquid-phase mediators, such as V3+, VO2+, and Fe(CN)64-, are commonly used in flow batteries. The advantages and limitations of high-pressure hydrogen production using decoupled water electrolysis are analyzed. Although the DWE system offers notable flexibility and safety, its electrolytic efficiency at high current densities still shows substantial space for improvement. This review provides valuable insights into optimizing high-pressure water electrolysis technologies and offers guidance for future research aimed at enhancing the performance and safety of high-pressure hydrogen production systems.