The materials' issue is one of the main bottlenecks restricting the development of nuclear energy systems. Based on the requirements of low activation, high-temperature thermal stability, high strength, high ductility, high thermal conductivity, irradiation resistance, corrosion resistance and other characteristics, the FeCrVTix medium-entropy alloys (MEAs) were designed for the working under extreme environments of the advanced nuclear energy systems. Here, thermodynamic calculation and coupling with the selection of low activation and functional elements and phase composition estimation, to MEAs are shown in the effort to design this kind of modern advanced alloy materials. Meanwhile, a kind of FeCrVTix (x=0, 0.05, 0.1, 0.2, 0.3) MEAs, as a model material, was prepared by arc melting and its above-mentioned properties were investigated. The results show that FeCrVTix MEAs have excellent properties and quite match the previous expected design, which have great potential for nuclear applications as structural materials. Most importantly, this novelty and proven method of alloy design based on the target requirements and configuration entropy has been proven to be correct and feasible, providing a new way for the design and rapid screening of new materials.