Mixture of hydrocarbon and carbon dioxide shows excellent cycle performance in Organic Rankine Cycle (ORC) used for engine waste heat recovery, but the unavoidable leakage in practical application is a threat for safety due to its flammability. In this work, a quantitative risk assessment system (QR-AS) is established aiming at providing a general method of risk assessment for flammable working fluid leakage. The QR-AS covers three main aspects: analysis of concentration distribution based on CFD simulations, explosive risk assessment based on the TNT equivalent method and risk mitigation based on evaluation results. A typical case of propane/carbon dioxide mixture leaking from ORC is investigated to illustrate the application of QR-AS. According to the assessment results, proper ventilation speed, safe mixture ratio and location of gas-detecting devices have been proposed to guarantee the security in case of leakage. The results revealed that this presented QR-AS was reliable for the practical application and the evaluation results could provide valuable guidance for the design of mitigation measures to improve the safe performance of ORC system. (C) 2017 Elsevier B.V. All rights reserved.