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The fires bring huge loss every year, a large number of firefighters and victims are seriously injured in fires and many of them even lost their lives. The aim of this work is to study on the thermal safety and discomfort of human body in fire environment using modeling and CFD methods. A transient multi-node human thermal model is developed for improving the simulation of thermoregulation in serious condition. Coupled with the human thermal model, a real shaped model of male body with 176 curved surfaces and more than 200 thousand cells, and real physical parameters was built. The CFD computation was taken using standard k-epsilon turbulence viscous model and discrete coordinate radiation model. A virtual room with 3.0m × 3.0m × 2.6m was built and series of fire with typical heat release rate were introduced as heat resource. The simulation was taken with 0.5 second time step. The prediction of thermal injury degree was considered with Stoll's and Takata's injury model based on data from model and CFD computation. The time for heat stroke, deeply injury and degrees of thermal comfort indices were compared, the prediction of thermal safety and discomfort was made. Furthermore, a ventilated, fire-resistant enclosure including a radiator is constructed to improve the experiment.