The　failure　mechanism　of　the　mega-sub　isolation　system　under　near-fault　ground　motions　is　studied　in　this　article.　90　suites　of　near-fault　ground　motions　collected　from　23　earthquakes　are　adopted　to　investigate　the　ground　motion　intensity　indices　applicable　for　the　mega-sub　isolation　system.　Then,　the　sensitivities　of　the　stochastic　responses　to　the　structural　parameters　are　analyzed　to　determine　the　representative　random　structural　parameters.　Furthermore,　considering　the　uncertainties　of　ground　motion　characteristics　and　structural　parameters,　the　seismic　fragility　is　analyzed　by　the　response　surface　method　in　order　to　obtain　the　failure　mechanism　of　this　system　under　near-fault　ground　motions.　Results　show　that　different　intensity　indices　have　various　correlation　coefficients　with　the　peak　responses　of　the　mega-sub　isolation　system.　The　correlations　of　acceleration-related　intensity　indices　are　the　worst,　whereas　the　correlations　of　displacement-related　intensity　indices　show　high　linearity.　The　sensitivities　of　the　structural　responses　are　weaker　to　the　sub-structure　story　stiffness　but　more　sensitive　to　the　sub-structure　story　mass　and　the　stiffness　and　damping　ratio　of　the　isolation　layer.　The　failure　probability　of　the　sub-structure　is　higher　than　that　of　the　mega-structure　under　near-fault　ground　motion.　While　in　the　collapse　state,　the　failure　probability　of　the　isolation　layer　is　greater　than　that　of　the　sub-structure.