As a proactive safeguard, inherent safety has been regarded as the top hierarchy for loss prevention and risk management due to its salient features in eliminating or significantly reducing risks at source rather than mitigating them by add-on protections. Simultaneously, various assessment tools have been developed for ranking and selecting inherently safer designs or modifications. However, there still lacks a metric that can systematically incorporate various hazardous factors, which may hinder most industries from utilizing it to a full extent. To address this limitation, this work developed a Systematic Inherent Safety Metric (SISM) for measuring the inherently safer modifications. Firstly, the conceptual framework of SIS was proposed based on 5M1E (man, machine, material, method, measurement, and environment). Subsequently, analytic hierarchy process and fuzzy comprehensive evaluation were adapted to conduct risk identification and assessment. Finally, taking chlorine liquefaction process as a case study, the applicability and efficacy of SIS were validated based on PDCA (plan-do-check-action) cycle. The results show that the SISM value has improved from the relatively dangerous (RD) to the relatively safe (RS) after implementing SIS, thus demonstrating that the revised design is inherently safer than the base design.