The design type of large-scale museum buildings is comprehensive and professional building, therefore numerous factors must be considered. Fire protection engineering is a crucial component of this design process. Given the unique usage function and spatial demands, current specifications may prove inadequate or unable to accommodate evolving technologies. Therefore, specialized fire protection designs must be developed and demonstrated. In the event of a fire, it is essential to fully consider the storage and protection of cultural relics, audience safety and evacuation, equipment control and preservation, and minimizing operational disruption. To ensure the scientific validity and feasibility of the design, it is necessary to conduct fire scene simulation and fire safety analysis. Taking the project in the North Branch of the Palace Museum as a case study, this paper elaborates on the technical process of fire scene simulation and fire safety analysis. The Topics covered in the paper include: fire design, establishing the fire scene, setting evacuation scenarios, conducting evacuation simulation analysis, simulating smoke dispersion, and making safety assessments, which can provide a technical reference for similar types of building design.