Soil　spatial　variability　at　different　supports　is　vital　in　the　seismic　performance　assessment　of　large-span　structural　systems,　including　sea-crossing　cable-stayed　(SCCS)　bridges.　This　study　systematically　investigates　the　influences　of　soil　spatial　variability　on　the　seismic　performance　of　SCCS　bridges.　In　particular,　the　uncertain　sites　consid-ering　soil　spatial　variability　are　developed　based　on　the　random　field　theory　and　Latin　Hypercube　Sampling　technique.　The　refined　3D　finite　element　model　of　a　representative　SCCS　bridge　considering　soil-structure　interaction　(SSI)　is　created　in　ABAQUS,　and　the　spatially　varying　seafloor　seismic　motions　(SVSSMs)　with　soil　uncertainties　are　stochastically　simulated.　The　tornado　diagram　sensitivity　analysis　method　is　leveraged　to　study　the　relative　sensitivity　of　each　soil　property　on　the　dynamic　responses　of　the　SCCS　bridge.　Finally,　the　component　and　system　fragility　curves　are　developed　with　and　without　considering　soil　spatial　variability.　The　results　show　that　soil　spatial　variability　can　significantly　influence　the　SVSSMs　and　SSI,　and　lead　to　large　variability　of　bridge　seismic　responses.　The　uncertainties　of　soil　shear　modulus　and　density　have　the　most　evident　effects　on　the　seismic　responses　of　SCCS　bridges.　Furthermore,　it　is　also　found　that　neglecting　the　soil　spatial　variability　would　underestimate　the　component　and　system　seismic　fragility　of　SCCS　bridges.