Silver cluster-assembled materials (SCAMs), by virtue of their tunable structure, accessible surface area and excellent stability, hold great promise as highly efficient catalysts. Herein, we report a new SCAM [Ag-12((SBu)-Bu-t)(6)(CF3COO)(3)(TPyP)](n) (denoted as Ag12TPyP) composed of a Ag-12 chalcogenolate cluster core stabilized by porphyrinic ligands. Ag12TPyP showed superior sulfur mustard simulant (2-chloroethyl ethyl sulfide, CEES) degradation efficiency and achieved a half lifetime (t(1/2)) of 1.5 min with 100% selectivity. The experimental results demonstrated that synergistic effects between the silver cluster and photosensitizer ligand promote the efficiency of the generation of singlet oxygen (O-1(2)), which accelerates the decontamination rate. Additionally, benefiting from strong affinity between the silver cluster and CEES, Ag12TPyP exhibits a CEES uptake of 74.2 mg g(-1). This work demonstrates that SCAMs offer a new route to the rational design of novel materials for the detoxification of mustard gas.