Self-assembly has emerged as a powerful approach to generating complex supramolecular architectures. Despite there being many crystalline frameworks reported in the solid state, the construction of highly soluble periodic supramolecular networks in a three-dimensional space is still a challenge. Here we demonstrate that the encapsulation motif, which involves the dimerization of two aromatic units within cucurbituril, can be used to direct the co-assembly of a tetratopic molecular block and cucurbituril into a periodic three-dimensional supramolecular organic framework in water. The periodicity of the supramolecular organic framework is supported by solution-phase small-angle X-ray-scattering and diffraction experiments. Upon evaporating the solvent, the periodicity of the framework is maintained in porous microcrystals. As a supramolecular€ion sponge €, the framework can absorb different kinds of anionic guests, including drugs, in both water and microcrystals, and drugs absorbed in microcrystals can be released to water with selectivity.