The concept of advanced Generation-2 reactors developed over the past decades has posed great pressure on the material performance at high temperatures and dose levels. Recently, a novel class of materials termed as high entropy alloys (HEAs) has attracted numerous attentions in the material community. Previous reports demonstrated that the face-centered-cubic (FCC) HEAs provide a novel way to increase irradiation tolerance by simply tuning the chemical complexity. Specifically, increasing the number of principle elements can effectively reduce mean free paths of electron and phonon, thus modifies the defect formation and delays defect evolution, leading to an enhanced irradiation resistance. However, the low-strength and the simple microstructure of the most studied single-FCC HEA limits their practical applications in advanced Gen-IV systems designed with a common feature of high operating temperature and damage level. In order to meet the requirements of high temperature and high dose of irradiation in the Gen-IV systems, dual-phase HEAs with “FCC+L12” structure is designed as the studied materials. The advantages of introducing coherent multicomponent nanoparticles (MCNPs) into HEAs are twofold. First, a good mechanical performance at high temperatures can be expected due to precipitation hardening. Second, a further improved irradiation resistance could be achieved, mainly due to the increment of sink strength (coherent phase boundaries) and also the controllable chemical complexity. Both of the above are crucial to the reliability of advanced nuclear energy applications.In order to have an in-depth understanding of the irradiation effects on the MCNP-strengthened HEAs, we will address three scientific issues in the present proposal. First, a quantitative evaluation of the irradiation-induced defects will be carefully carried out. Second, irradiation-induced segregation (RIS) in preferential regions such as grain boundaries, dislocations and voids will be studied through the combination of atom probe tomography (APT) and transmission electron microscope (TEM) analyses. The underlying segregation mechanisms will be discussed. Third, we tend to further assess the phase stability of the multicomponent nanoparticles in the MCNP-strengthened HEAs under irradiation. In particular, the stability of the MCNPs with different chemical constitution will be explored and the origin of those behaviors will be further explained.The successful fulfillment of this proposal will lead to a comprehensive understanding of the irradiation behaviors of the MCNP-strengthened HEAs under extreme environments. The outcomes will provide an effective guidance for the accelerated design of irradiation-tolerated HEAs for advanced nuclear applications.