This paper uses probability method to evaluate the fire safety performance of prestressed steel-concrete beam bridges based on simulation experimental research. Firstly, fire simulation experimental sample analysis was conducted on actual small box girder bridges to obtain the structural response of prestressed steel-concrete structures under fire, which is in line with engineering practice. Next, construct a reliability analysis model for the fire resistance performance of prestressed steel-concrete beam bridges; Combining reliability theory with finite element method, establish a reliability analysis method for the fire resistance performance of prestressed steel-concrete beam bridges. Subsequently, a safety factor evaluation model for the fire resistance performance of prestressed steel-concrete beam bridges was proposed, and a safety factor evaluation method for the fire resistance performance of prestressed steel-concrete beam bridges based on reliability back analysis was established. Finally, based on the analysis of the structural response after a fire in a specific case of a simply supported to continuous prestressed steel-concrete continuous beam bridge project, a structural resistance sample of the prestressed steel-concrete beam bridge is generated through uniform design method, and statistical analysis is conducted. Subsequently, probability methods are used to evaluate the safety of the prestressed steel-concrete beam bridge after a fire. Through analysis, it can be concluded that the time of fire has a significant impact on the structural performance of prestressed steel-concrete beam bridges, and the randomness of parameters has a significant impact on the safety reserve of prestressed steel-concrete beam bridges after fire. It is necessary to pay attention to it in specific engineering practice and strengthen the monitoring and statistics of structural random characteristics.