The supercritical carbon dioxide (sCO2) Brayton cycle demonstrates special advantages for the high temperature gas-cooled reactor (HTGR) delivered into commercial operation recently in China, with its high efficiency, compactness, flexibility, and safety compared to the conventional steam Rankine cycle. However, the large temperature rise of 500 °C for the HTGR brings new challenges for the design of sCO2 cycle. Here, we present the first study on the thermodynamic, economic, and environmental performance of the HTGR-sCO2 system using the energy, exergy, economic, and environmental (4E) evaluation method. The cascaded sCO2 cycle made up of two independent sCO2 cycles is proposed, which are arranged in series on the cold side of reactor heat exchanger. We show that the cascaded sCO2 cycle can utilize the heat absorption from HTGR effectively by optimizing the cycle configurations of top and bottom sub-cycles. The improved cascaded sCO2 cycle minimizes the exergy loss, and increases the thermal efficiency to 43.2% when compared to the steam Rankine cycle of HTGR demonstration power plant and the single recompression cycle. By balancing the fixed-capital investment cost with the net power, the levelized cost of electricity can be reduced to 0.0283$/kWh. The life-cycle GHG emission intensity of HTGR-sCO2 systems is about 6.5gCO2,eq/kWh, which is much smaller than that of coal-fired power plants, suggesting a great potential for decarbonization of the HTGR-sCO2 system. Our study may find implications for the advancement of the sCO2 Brayton cycle in next-generation nuclear power plant.