Reactor system which applies supercritical carbon dioxide(s-CO2) Brayton Cycle as its direct power conversion system has advantages of high thermal efficiency and high compactness. Due to the high coolant outlet temperature (around 500 °C) and the less effective heat transfer capacity of S-CO2 compared to water or metal liquid, which are commonly used in GEN IV reactor concepts, the safety performance of this kind of newly developed reactor system needs to be carefully evaluated. Preliminary safety assessment of loss-of-flow accident (LOFA) for a s-CO2 Brayton cycle cooled reactor system is carried out in this paper. The safety analysis methodology is proposed firstly and three types of LOFA are investigated to clarify the unique safety characteristics of s-CO2 Brayton cycle cooled reactor system, including partial LOFA with reactor scram, partial LOFA without reactor scram and total LOFA. The short term analysis results demonstrate that the reactor core can survive these three types of LOFA without safety system in the very first 10 to 20 s. A hybrid passive/active emergency core cooling system is designed to remove the decay heat for a long time. Results indicate that the hybrid passive/active emergency core cooling system designed in this paper can help the reactor system safely go through these three types of LOFA. This study will be benefit for the core design and safety system design for s-CO2 direct cooled rector system.