In factories where high-risk chemical pollutants are treated, it is essential to anticipate response measures in the event of chemical pollutant leakage to minimize adverse health effects on workers. When high-risk liquid chemical pollutants are assumed to be leaked inside enclosed spaces, it becomes crucial to predict the non-uniform concentration distributions in enclosed spaces and evaluate the health impacts and risks of short-time exposure to prevent large-scale accidents. Therefore, we have developed an emergency ventilation system for controlling the inhaled contaminant dose of factory workers. In this study, assuming a worst-case scenario liquid chemical pollutant leak in an enclosed factory space, the advantages and performance of a hybrid ventilation system that combines displacement and push–pull type ventilation systems were numerically investigated. Installation of wall materials that facilitate photocatalytic oxidation (PCO) reactions for background passive concentration control was also discussed. Based on the demonstrative numerical analyses for a realistic factory space, push–pull type ventilation system was confirmed to effectively suppress chemical pollutant diffusion in enclosed spaces with a low ventilation rate. Wall materials with the PCO mechanism had a certain contribution to the control of peak concentration.