A methodology to evaluate the seismic performance of interface piping systems that cross the isolation interface in the seismically isolated nuclear power plant (NPP) was developed. The developed methodology was applied to the safety-related interface piping system to demonstrate the seismic performance of the target piping system. Not only the seismic performance for the design level earthquakes but also the performance for the beyond design level earthquakes were evaluated. Two artificial seismic ground input motions which were matched to the design response spectra and two historical earthquake ground motions were used for the seismic analysis of piping system. The preliminary performance evaluation results show that the excessive relative displacements can occur in the seismically isolated piping system. If the input ground motion contained relatively high energy in the low frequency region, we could find that the stress response of the piping system exceed the allowable stress level even though the intensity of the input ground motion is equal to the design level earthquake. The structural responses and seismic performances of piping system were varied sensitively with respect to the intensities and frequency contents of input ground motions. Therefore, for the application of isolation system to NPPs and the verification of the safety of piping system, the seismic performance of the piping system subjected to the earthquake at the target NPP site should be evaluated firstly.