A novel, effective and simple surface-enhanced Raman scattering (SERS) nanosensor for selectively and sensitively detecting heavy metal ions in aqueous solution has been developed in the form of 2-mercaptoisonicotinic acid (2MNA)-modified gold nanoparticles (AuNPs). Multiple heavy metal ions can be identified and quantified by using relative peak intensity ratios of selected vibrational bands in the SERS spectra of 2MNA. Especially, concentration of Hg 2+ and Pb 2+ ions are determined by comparing the intensity ratios of the bands 1160/1230cm −1 for Hg 2+ and 861/815cm −1 (or 815/1392cm −1 ) for Pb 2+ , with detection limits of 3.4×10 −8 and 1.0×10 −7 M, respectively. 2MNA–AuNPs sensors show a high selectivity for Hg 2+ without masking reagent, and they can also be highly selective for Pb 2+ when using sodium thiosulphate and l-cysteine as masking reagents. These results demonstrate that these 2MNA–AuNPs nanosensors are promising candidates for in situ heavy metal ions detection and quantification, maybe even inside living cells.