“Aggregation-caused　signal　change”,　a　well-established　mechanism,　should　not　be　ignored　for　sensing,　while　small　molecule　based　on　self-assembly　and　disaggregation　has　been　studied　and　used　for　protein　detection.　In　this　work,　we　have　synthesized　a　novel　fluorescent　chemosensor　SQ　with　a　polyether　chain　to　enhance　water　solubility,　and　this　has　been　used　for　the　detection　of　human　serum　albumin　(HSA)　in　aqueous　solution　with　excellent　sensitivity　and　selectivity.　SQ　was　aggregated　into　nanoparticles　with　an　average　particle　size　of　458　nm　in　neutral　solution　and　showed　fluorescence　silent　due　to　the　aggregation-induced　quenching.　However,　addition　of　HSA　decreased　the　average　particle　size　of　SQ　to　295　nm　and　released　the　fluorescence　because　of　the　reassembly　of　the　SQ-HSA　complex.　More　importantly,　HSA　could　be　selectively　detected　in　the　presence　of　other　biological　proteins　and　the　main　physiological　inorganic　anions　and　cations　with　the　detection　limit　estimated　as　15.6　nM　according　to　3σ/k.　This　versatile　strategy　suggests　that　squaraine　dyes　can　be　used　as　fluorescence-enhanced　probes　for　the　quantitative　detection　of　HSA　as　well　as　in　applications　for　the　detection　of　HSA　in　urine　samples.　©　2017　Elsevier　B.V.