Yes / Process safety has drawn increasing attention in recent years and has been investigated from different perspectives, such as quantitative risk analysis, consequence modeling, and regulations. However, rare attempts have been made to focus on inherent safety design assessment, despite being the most cost-effective safety tactic and its vital role in sustainable development and safe operation of process infrastructure. Accordingly, the present research proposed a knowledge-driven model to assess inherent safety in process infrastructure under uncertainty. We first developed a holistic taxonomy of contributing factors into inherent safety design considering chemical, reaction, process, equipment, human factors, and organizational concerns associated with process plants. Then, we used subject matter experts, content validity ratio (CVR), and content validity index (CVI) to validate the taxonomy and data collection tools. We then employed a fuzzy inference system and the Extent Analysis (EA) method for knowledge acquisition under uncertainty. We tested the proposed model on a steam methane-reforming plant that produces hydrogen as renewable energy. The findings revealed the most contributing factors and indicators to improve the inherent safety design in the studied plant and effectively support the decision-making process to assign proper safety countermeasures.