Abstract: The second stage beamline design was carried out for the single-event-effect irradiation device on the 100 MeV proton cyclotron of China Institute of Atomic Energy. The beam was expanded and homogenized by the octupole magnet correction method, and finally a 30 cm×30 cm beam spot with a uniformity better than 92% was obtained on the target, which meeting the need of single-event-effect experiments. In order to reduce the energy dispersion and the neutron background at the target station, a twostage energy reduction scheme was adopted. A degrader was placed in front of the deflection magnet, and the energy was divided into two levels of 100 MeV and 40 MeV, respectively. The beamline scheme under the two energy points was designed and the beam utilization rate is above 42%. The results of the tolerance analysis show that the influence of the quadrupole magnet on the uniformity of the beam spot for the target is greater than that of the octupole magnet, and the installation tolerance of the quadrupole magnet should be given priority during the installation process.