Fluoride is important to explore because it plays important roles in nature and biological processes. To accomplish selective F⁻ sensing in aqueous solution, a nanochannel modified with 1,3-dipropargylaza-p-tert-butyl calix[4]crown (C4CE) was designed on the basis of hydrogen-bonding interactions. The nanodevice not only exhibits high selectivity for F⁻, even in serum, but also shows the useful property of recyclability.