A polyoxovanadate-based nickel-organic framework, [Ni(bib)2]{V2O6}({V6}-MOF, bib = 1,4-bis(1H-imidazoly-1-yl)benzene), was facilely prepared under gentle hydrothermal conditions and structurally characterized. Single-crystal X-ray diffraction analysis indicates that the {V6} cluster in the {V6}-MOF is constructed of two VO5 tetragonal pyramids and four VO4 tetrahedrons via the apex sharing of O atoms, presenting a hollow Linqvist-like structure, which is different from these reported hexanuclear vanadium clusters. The {V6}-MOF not only expands the structure of polyoxovanadates (POVs) but also catalyzes the rapid detoxification of mustard gas simulant (2-chloroethyl ethyl sulfide, CEES) at 25 °C. The catalytic results were determined by means of GC, GC-MS, and 1H NMR. Using {V6}-MOF as a heterogeneous catalyst, CEES underwent catalyzed oxidation to only nontoxic product 2-chloroethyl ethyl sulfoxide (CEESO) within 40 min, and the conversion and selectivity were almost 100%. In addition, {V6}-MOF exhibits high sustainability, and no obvious reductions in conversion and selectivity are observed after five runs.