Liquid water is essential for life, but many other substances that exist in the liquid state under standard conditions can have severe detrimental effects on living organisms and the environment. Isolation of these substances and determination of their three-dimensional structures are important to understand and, ultimately, to eliminate their harmful effects. Unfortunately, the mobility and disorder inherent in liquid molecules present major challenges for their structure elucidation. Consequently, very few structures of liquid molecules have been determined with certainty. Here, a hexazirconium-based MOF [ZrFMOF, Zr ₆(μ ₃-O) ₈(COO) ₈(H ₂O) ₈(DEF) ₇] was synthesized and shown to act as a host framework to capture and facilitate the crystal structure determination of a series of liquid molecules. In this respect, the ZrFMOF serves as a robust pre-organized single crystalline coating (PSCC) material on the target guest. The ZrFMOF successfully encapsulated 12 toxic liquid molecules through weak interactions within two binding cavities (A and B), enabling accurate structural determination of individual guest molecules, two mixtures and an unknown liquid, all without the need for activation. Three distinct binding modes were identified, involving cavities A, B and A and B together. Furthermore, the ZrFMOF showed excellent adsorption capacities on iodine, various dyes and polyfluoroalkyl substances (PFAS), which was confirmed by solid-state NMR. In particular, the ZrFMOF has been so far the strongest absorbent on PFAS (absorption capacity: 1.23 mg mg ⁻¹). In summary, it is demonstrated for the first time that the ZrFMOF is a versatile PSCC material that can be used to sequester and identify a range of toxic liquid molecules and remove three kinds of pollutants (iodine, dyes and PFAS) in water.