Selective uptake and elution of trace amounts of hazardous radioactive 90Sr from large-scale high-level liquid waste (HLW) is crucial for sustainable development. Here, we propose a site differentiation strategy, based on the presence of distinct selective metal capture sites (concavity site and tweezer site) within the giant polyoxoniobate (PONb) nanoclusters of an all-inorganic PONb framework (FZU-1). Through this strategy, FZU-1 can not only effectively remove 98.9% of Sr²⁺ from simulated nuclear liquid waste, performing best among the reported Sr adsorbents, but also achieve desorption of adsorbed Sr²⁺ ions by selectively loading Na⁺ ions, thus enabling the recycling of FZU-1. Based on the well-defined single-crystal structures and theoretical studies, it can be revealed that the rapid and selective uptake of Sr²⁺ is attributed to the strong binding energy between the Sr²⁺ ions and the concavity sites. The effective elution of Sr²⁺, on the other hand, stems from the preferential binding of Na⁺ ions at the tweezer sites, elevating the cluster's electrostatic potential and indirectly facilitating the elution of Sr²⁺ ions. The exceptional stability of FZU-1, along with its rapid and selective Sr²⁺ capture and elution capabilities, positions it as a promising candidate for large-scale nuclear waste treatment and groundwater remediation applications. Here, the authors propose a site differentiation strategy in ion exchange, that is, functional materials with different adsorption sites for specific metal ions can achieve efficient uptake and elution of specific ions (e.g., Sr2+ ion in this work).