In this study, fluorescent metal nanoshells were synthesized as a molecular imaging agent to detect single microRNA (miRNA) molecules in the cells positive to lung cancer. These metal nanoshells were composed of silica spheres with encapsulated Ru(bpy)(3)(2+) complexes as cores and thin silver layers as shells. Compared with the silica spheres in the absence of metal, the metal nanoshells displayed an enhanced emission intensity, shortened lifetime, and extended photostability. The single-stranded probe oligonucleotides were covalently bound on the metal nanoshells to hybridize with the target miRNA-486 molecules in the cells. It was shown that with stronger emission intensity and longer lifetime, the conjugated metal nanoshells were isolated distinctly from the cellular autofluorescence on the cell images. These emission spots on the cell images were counted accurately and analyzed with a pool of cells representing the miRNA-486 expression levels in the cells. The results may reflect a genomic signal change and provide a reference to lung cancer early diagnosis as well as other diseases.