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Abstract The selective and efficient monitoring of mercury (Hg2+) contamination found in the environment and ecosystem has been carried out. Thus, a new 1,8‐naphthalimide‐based fluorescent probe NADP for the detection of Hg2+ based on a fluorescence enhancement strategy has been designed and synthesized. The NADP probe can detect Hg2+ with high selectivity and sensitivity and a low detection limit of 13 nm. The detection mechanism was based on a Hg2+‐triggered deprotection reaction, resulting in a dramatic change in fluorescence from colorless to green at physiological pH. Most importantly, biological investigation has shown that the NADP probe can be successfully applied to the monitoring of Hg2+ in living cells and zebrafish with low cytotoxicity.