The　widespread　application　of　metal-organic　frameworks　(MOFs)　is　seriously　hindered　by　their　structural　instability　and　it　is　still　very　challenging　to　probe　the　stability　of　MOFs　during　application　by　current　techniques.　Here,　we　report　a　novel　structure-responsive　mass　spectrometry　(SRMS)　imaging　technique　to　probe　the　stability　of　MOFs.　We　discovered　that　intact　CuBTC　(as　a　model　of　MOFs)　could　generate　the　characteristic　peaks　of　organic　ligands　and　carbon　cluster　anions　in　laser　desorption/ionization　mass　spectrometry,　but　these　peaks　were　significantly　changed　when　the　structure　of　CuBTC　was　dissociated,　thus　enabling　a　label-free　probing　of　the　stability.　Furthermore,　SRMS　can　be　performed　in　imaging　mode　to　visualize　the　degradation　kinetics　and　reveal　the　spatial　heterogeneity　of　the　stability　of　CuBTC.　This　technique　was　successfully　applied　in　different　application　scenarios　(in　water,　moist　air,　and　CO2)　and　also　validated　with　different　MOFs.　It　thus　provides　a　versatile　new　tool　for　better　design　and　application　of　environment-sensitive　materials.　©　2024　The　Royal　Society　of　Chemistry.