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[Display omitted] • The sensor is highly sensitive and selective to Hg2+ with low detection limit. • The sensor provides five cycles–reversibility for Hg2+ detection. • The sensor offers a very large Stokes shift of 192 nm. • The sensor enables for quick screening of Hg2+ in water and cosmetic samples. • Application in the potential Hg2+–accumulated human cells is demonstrated. Mercury pollution and its toxicity pose a grave threat to health. Therefore, developing new approaches for detecting mercury ions (Hg2+) in environmental and biological samples is crucial. Herein, a novel [5]helicene-based fluorescence sensor (M201NHP) was designed and synthesized for rapid, sensitive and specific detection of Hg2+. The sensor exhibits fluorescence quenching with a very large Stokes shift (192 nm) towards Hg2+ in aqueous acetonitrile media. The detection limit of the sensor is estimated to be 1.94 ppb, which is lower than the U.S. EPA specification for the maximum Hg2+ level in drinking water. Moreover, M201NHP offers five cycles of reversibility upon competitive chelation of cysteine. The sensor can also screen for Hg2+ contamination in real water samples and skincare products. Additionally, it can track Hg2+ in potential mercury-accumulated human cell lines derived from brain tumours, embryonic kidneys, skin and liver cancers with low cytotoxicity. These results indicate that M201NHP is a promising Hg2+ sensor that can prevent health risks and environmental impacts caused by mercury pollution. [ABSTRACT FROM AUTHOR]