We designed and fabricated the nanomechanical Pb(Zr 0.52 Ti 0.48 )O 3 (PZT) cantilever; we demonstrated a novel electrical measurement, under a controlled ambient temperature and humidity, for label-free detection of a prostate-specific antigen (PSA); and we achieved a detection sensitivity as low as 10pg/ml. For the fabrication of our nanomechanical PZT cantilevers, we used composite layers of Ta/Pt/PZT/Pt/SiO 2 on a SiN x supporting layer for electrical self-sensing without external oscillators. This method allows PSA proteins to be detected via a simple electrical measurement of the resonant frequency change generated by the molecular interaction of the antigen (Ag) and the antibody (Ab). The resonant frequency shifted due to the specific binding of the PSA Ag to its Ab which is immobilized via calixcrown self-assembled monolayers on an Au surface deposited on a nanomechanical PZT cantilever. We determined the resonant frequency shift as the value of −172Hz and −273Hz, when the concentration of PSA Ag was 1ng/ml, with the cantilever dimensions of 100μm×300μm and 50μm×150μm, respectively. Theoretical and experimental analysis suggests that the minimum detectable sensitivity for a resonant frequency shift due to a PSA Ag–Ab interaction depends on the dimensions of the nanomechanical PZT cantilever. These results also demonstrate that the experimentally measured resonant frequency shift is larger than that calculated theoretically due to the compressive stress of the PSA Ag–Ab interaction.