To accurately assess the navigation safety status of LNG vessels in port waters and balance safety control with waterway capacity efficiency, this study constructs a 3D dynamic safety domain model for port LNG vessels, integrating human–ship–environment multi-factors. The model introduces the Weibull function to quantify the impact of drivers’ knowledge, skills, and physiological-psychological states on safety boundaries, combines a ship motion mathematical model to establish a 2D safety domain boundary equation, and incorporates hull subsidence to build a vertical dimension, forming a complete 3D model. Longitudinally, the safety distance is calculated using the car-following braking theory, while laterally, boundaries are determined by controlling the ratio of inter-vessel interference force to navigation resistance. Through static scenario analysis and dynamic simulation verification, results show that the safety domain scale is dominated by ship speed and environmental conditions, and its shape tends to shrink as the driver’s state improves, making it more suitable for actual port scenarios than traditional models. Verified with a specific LNG hub port as a case, the safety distance calculated by the model is significantly reduced compared with current specifications, while the delay impact rate and average delay time on other vessels are decreased. The research results establish a quantifiable framework for dynamic safety assessment, providing maritime administrations and on-board pilots with a scientifically-grounded tool to determine real-time safe navigation boundaries in complex port environments, balancing safety control with operational efficiency.