MicroRNA (miRNA), an 18-24-nucleotide (nt) noncoding RNA molecule in the genes of humans, plants and animals, is emerging as a key player in gene regulation. As a result, label-free, rapid, and sensitive detection for miRNA is of great significance. In this work, a label-free and direct hybridization assay for ultrasensitive detection of miRNA using silicon nanowires (SiNWs) device has been developed. Peptide nucleic acids (PNAs), which serve as a receptor to recognize miRNA directly without labeling the target miRNA, are immobilized on the surface of the SiNW device. Resistance change measured before and after hybridization correlates directly to concentrations of the hybridized target miRNA. Concentration-dependent measurements indicate that a detection limit of 1 fM was obtained using the optimized assay. The technique enables identification of fully matched versus mismatched miRNA sequences. Furthermore, the SiNW device is capable of detecting miRNA in total RNA extracted from Hela cells. This approach paves a way for label-free, early detection of miRNA as a biomarker in cancer diagnostics with very high sensitivity and good specificity. © 2008 Elsevier B.V. All rights reserved.