Abstract: A new type of long-span spatial steel frame was used for Guangdong Science Center ( GSC) ． The isolation techniques are introduced into the E square of GSC to protect the huge building from damage during external loads， especially typhoon and earthquake，and ensure the safety of people，exhibits and instruments in the building． Isolating bearings were directly placed on the base of the columns． The non-linear dynamic analysis and shaking table tests were used to study the vibration reduction effect of the model with base isolation contrasting to the structure without base isolation，evaluate the improvement degree of the earthquake-resistance capability，and estimate the rationality of the isolation methods by the effect of the bearings on the performance harmony of column deformation． It was shown by the study that the isolation methods could obviously improve the earthquake-resistance capability of the building，modify the torsion performance and enhance the safety during severe earthquakes more markedly，especially for the structures with irregular space． Additionally，isolation bearings had no negative effect on the performance harmony of column deformation for the stiffness． The isolation design methods of GSC were rational，and could be an useful effort for isolation design of large-scale spatial structures．