This　article　describes　the　rational　design　and　synthesis　of　a　monothiosquaraine　(MTSQ)　fluorescent　Hg2+　probe　that　exhibits　near-infrared　fluorescence,　ultrahigh　brightness,　fast　response,　high　sensitivity　and　excellent　selectivity.　Utilizing　the　strategy　of　the　incorporation　of　the　heavy　atom　effect　and　self-assembly　caused　quenching,　the　background　fluorescence　of　MTSQ　was　greatly　lowered　and　the　sensitivity　in　PBS　buffer　solution　was　highly　enhanced　with　a　very　low　limit　of　detection　(LOD　=　1.2　nM).　Systematic　studies　revealed　excellent　selectivity　and　specificity　for　Hg2+　over　other　thiophilic　metal　ions　such　as　Ag+,　Pb2+,　and　Cd2+.　The　mechanistic　investigation　indicates　that　self-assembly　and　desulfurization　of　MTSQ　are　responsible　for　Hg2+-triggered　significantly　higher　fluorescence　enhancement.　With　high　sensitivity,　optimal　pH　range　of　3–7,　weak　background,　good　water-solubility　and　low　cytotoxicity,　MTSQ　therefore　can　be　applied　for　imaging　Hg2+　in　live　cells　and　zebrafish.　The　very　simple　but　effective　strategy　reported　here　can　provide　a　more　convenient　approach　for　designing　NIR　probes.　©　2018　Elsevier　Ltd