The separation of xenon/krypton (Xe/Kr) mixtures plays a vital role in the industrial process of manufacturing high-purity xenon. Compared with energy-intensive cryogenic distillation, porous materials based on physical adsorption are very promising in the low-cost and energy-saving separation processes. Herein, we show that a cationic metal-organic framework (named as FJU-55) exhibits highly efficient Xe/Kr separation performance, which can be attributable to its uniform three-dimensional (3D) interconnection channels and the electro-positive features as the host framework. Moreover, FJU-55 demonstrates good Xe adsorption capacity of 1.41 mmol/g and excellent Xe/Kr selectivity of 10 (298 K and 100 kPa), together with a high Q_st value of 39.4 kJ/mol at low coverage area. The superior Xe/Kr separation performance of FJU-55 was further confirmed by the dynamic breakthrough experiments. Results obtained via molecular modeling studies have revealed that the suitable pore size and abundant accessible aromatic ligands in FJU-55 could offer strong multiple C–H∙∙∙Xe interactions, which play a collaborative role in this challenging gas separation task.