Working with volatile chemicals creates numerous hazards for scientists in laboratory. Therefore, it is restricted to do such works in a fume hood, which is designed to draw fresh air from the room into the hood and then out into the ventilation system, in order to prevent the accidents happened. According to the laboratory fire incidents investigation, the authors observed that a fire occurred in fume hood will be a serious problem which has the potential to get much worse in the future as more and complex laboratories are used and as the hood usage density increase. In this paper, the authors conducted the numerical experiments by using 3D Computational Fluid Dynamics (CFD) method to evaluate the fire extinguish performance of CO 2 system in fume hood. The simulation results showed that the position of CO 2 nozzle, exhaust air volume, position of sash had a significant effect on fire extinguish in hood. The innovative hybrid system combined fire extinguish system and local exhaust system was designed to ensure the flow pattern in hood could be well-controlled to prevent the contaminant leakage from hood sash as the CO 2 system is activated.