Nickel-graphene nanolayers with high-density interfaces are expected to have excellent resistance to helium (He) embrittlement and proposed as candidate materials for molten salt reactor systems. However, He irradiation effects on nickel-graphene nanolayers remains poorly understood at present. In this work, the influence of a nickel-graphene interface (NGI) on the nucleation and growth of He-related clusters was studied by using atomistic simulations. The NGI reduces formation energies and diffusion energy barriers for He-related clusters. The reduction makes He-related clusters easily be trapped by the interface, thus leading to significant segregation. Consequently, He concentration in the bulk is considerably reduced, and the nucleation and growth rates of He-related clusters in the bulk are delayed. Owing to the high mobility of He-related clusters at the NGI, these clusters easily coalesce to form larger clusters than those in the bulk. A reasonable design of nanolayers may promote He releasing from materials. Results of the current study can provide fundamental support for the service life assessment of nickel-graphene nanolayers in extreme environments.