A novel, label-free DNAzyme-based quartz crystal microbalance with dissipation monitoring (QCM-D) biosensor was developed for the highly sensitive and specific detection of Pb(2+) ions. To enhance the performance of the sensor, oligonucleotide-functionalized gold nanoparticles were used for both frequency and dissipation amplification. This sensor was developed by immobilizing Pb(2+)-specific DNAzymes onto the QCM-D sensor surface and allowing them to hybridize with substrate-functionalized AuNPs. The DNAzyme catalyzed the cleavage of the substrate in the presence of Pb(2+) ions, causing the cleaved substrate-functionalized AuNPs to be removed from the sensor surface. Thus, Pb(2+) ions can be determined on-line by monitoring the change in frequency and dissipation signals. The results revealed that the sensor showed a sensitive response to Pb(2+) ions with detection limits of 14 nM and 20 nM for frequency and dissipation, respectively. This QCM-D biosensor also exhibited excellent selectivity toward Pb(2+) ions in the presence of other divalent metal ions. In addition, the approach was able to detect Pb(2+) in tap water, demonstrating its great potential for monitoring drinking water quality. The proposed sensor system described here represents a new class of lead ion sensor. Its simple detection strategy makes it feasible for 'pollution-free' detection; thus, the approach could have applications in on-line water quality monitoring.