Seismic fragility analysis can accurately estimate seismic performance of a structure, to propose a method to study on the seismic fragility of space grid structure, the full-load field time-history analysis, parameter sensitivity analysis and seismic fragility analysis were carried out. The results show that space grid structure has a ductile damage with obvious signs. The responses of this kind of structure are more sensitive to steel yield strength, floor loads and ground motion records, which can be considered as random factors in subsequent analysis. The seismic damage index and damage grading standard, which are applicable to orthogonal pyramid space grid, were proposed based on the seismic response of whole process. According to the seismic fragility analysis, the probability of ensuring intactness at PGA=0.40g is 95%, while 79% at PGA=0.62g. The orthogonal pyramid space grid has a good seismic performance, which can largely ensure the seismic safety.