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Hot-rolled Ni-201/Inconel 617 bimetal composite plate with excellent high-temperature strength has acquired significant attention in molten salt reactors (MSRs). To evaluate its potential applications, this alloy was irradiated by He ions at 650, 750, and 850 °C to study their irradiation performance, especially the hot-rolled interface. The scanning electron microscope (SEM) shows that some precipitates distribute along the micro-scale hot-rolled interface. The transmission electron microscopy (TEM) results indicate that the thickness of alloy elements diffusion layer around the interface increase with the increasing temperature, which can enhance their combination. Additionally, the lower helium swelling values are observed in the hot-rolled interface, which suggests that the hot-rolled interface has better resistance to swelling. The presence of TiN/Cr23C6 has a stronger ability to trap He atoms and inhibit their diffusion to the hot-rolled interface, which can improve the swelling resistance of the interface. The variation of nanohardness around the hot-rolled interface after irradiation reveals that the hot-rolled interface exhibits better resistance to irradiation-induced hardness than Inconel 617 side. Therefore, Ni/Inconel 617 alloy with promising resistance to swelling has a great potential to function for high-temperature MSRs.