<p>The&#xa0;nanozyme Cu5-ClNA with laccase-like activity was prepared&#xa0;by coordinating 5-chloronicotinic acid (5-ClNA) as a ligand with Cu²⁺. Further modification of Cu5-ClNA using 2,3,5,6-tetrafluorophenylthiophenol (TFTP) yielded the fluorescent nanozyme Cu5-ClNA-TFTP with enhanced laccase-like activity simultaneously. The resulting Cu5-ClNA-TFTP exhibited superior laccase-like activity with a higher maximal velocity (<i>V</i>_<i>m</i> = 3.504&#xa0;µM/min) and a lower Michaelis constant (<i>K</i>_<i>m</i> = 0.177&#xa0;µM). In addition, the fluorescent nanozyme Cu5-ClNA-TFTP showed differential sensing of three dihydroxybenzene isomers and selective detection of catechol (CC) and hydroquinone (HQ). The selective detection of CC and HQ respectively was realized without the interference of resorcinol (RC). CC was detected with a low&#xa0;limit of detection (LOD = 0.016&#xa0;µg/mL) due to the fluorescence burst of Cu5-ClNA-TFTP that can be quenched by quinones. Detection of HQ was performed by a distinct shift in fluorescence color from red to green with an LOD of 0.028&#xa0;µg/mL. The method also achieved good detection results in real environmental water bodies and provided a new method for selective detection of CC and HQ.</p> Graphical Abstract <p></p>