In this communication, biocompatible cadmium selenium quantum dots (CdSe QDs)-chitosan (CS) nanocomposites for fluorescence detection of nitric oxide (NO) are reported. The QDs-CS nanocomposites were generated by in situ synthesizing CdSe QDs in a CS aqueous solution, having spherical outline and an average dimension of 386.4 nm. Almost all the CdSe QDs, with the dimension from 5 to 12 nm, distribute well in the CS matrix. Many of the CdSe QDs are very close to the surface of the QDs-CS nanocomposites, in favor of the detection of NO. The QDs-CS nanocomposites are sensitive to NO molecules and can detect NO based on fluorescence quenching by NO, as evidenced by fluorescence microscopy and photoluminescence (PL) spectroscopy. The QDs-CS nanocomposites have potential biomedical applications owing to their low cytotoxicity. (C) 2012 Elsevier B.V. All rights reserved.