In the design of nuclear power plant pipeline system, PIPESTRESS software is usually used for pipeline stress calculation to meet the design requirements of ASME code (ASME Code 1989 edition [1]). However, PIPESTRESS cannot simulate the support effect of nonlinear pipe support under dynamic load. This paper takes the pipeline system of a nuclear island building of a nuclear power plant as the analysis object. In this system, two squib valves are arranged and three non-linear supports are used as valve supports. The system process analysis shows that the squib valves will generate significant dynamic loads when actuation, which makes the stiffness of the pipeline and valve supports very sensitive during strength analysis, the nonlinear effect of the valve supports needs to be considered. In order to more accurately evaluate the structural integrity and functionality of the pipeline system under the effect of dead weight, thermal expansion, earthquake and hydrodynamic load generated by valve actuation, a pipeline model was established using PIPESTRESS software to calculate the stress of the pipeline system under dead weight, thermal expansion, and seismic loads. A pipeline model considering nonlinear support effects was established using ANSYS software to calculate the pipeline stress under valve actuation load, and finally evaluate the results of the two analysis methods in combination. The comprehensive application of two calculation methods makes the calculation results more realistic, which is of great significance to ensure the safe operation of nuclear equipment in nuclear power plant.