The current industrial environment relies heavily on maritime transportation. Despite the continuous technological advances for the development of innovative safety software and hardware systems, there is a consistent gap in the scientific literature regarding the objective evaluation of the performance of maritime operators. The human factor is profoundly affected by changes in human performance or psychological state. The difficulty lies in the fact that the technology, tools, and protocols for investigating human performance are not fully mature or suitable for experimental investigation. The present research aims to integrate these two concepts by (i) objectively characterizing the psychological state of mariners, i.e., mental workload, stress, and attention, through their electroencephalographic (EEG) signal analysis, and (ii) validating an innovative safety framework countermeasure, defined as Human Risk-Informed Design (HURID), through the aforementioned neurophysiological approach. The proposed study involved 26 mariners within a high-fidelity bridge simulator while encountering collision risk in congested waters with and without the HURID. Subjective, behavioral, and neurophysiological data, i.e., EEG, were collected throughout the experimental activities. The results showed that the participants experienced a statistically significant higher mental workload and stress while performing the maritime activities without the HURID, while their attention level was statistically lower compared to the condition in which they performed the experiments with the HURID (all p < 0.05). Therefore, the presented study confirmed the effectiveness of the HURID during maritime operations in critical scenarios and led the way to extend the neurophysiological evaluation of the HFs of maritime operators during the performance of critical and/or standard shipboard tasks.