A new fluorogenic probe for fluoride anion detection was designed and synthetized accomplishing by the linkage between a Coumarin-440 and a Boc-Ser(TBDMS)-OH via amide bond formation. The photophysical properties and the selectivity for fluoride detection, among a range of anions (Cl−, Br−, I−, BF4 −, NO3 −, ClO4 −, PF6 −, HSO4 −, CN−, OAc−), was explored. The sensing mechanism was proposed and supported by 1H NMR and MALDI-MS experiments. A reaction triggered by the nucleophilic attack of the fluoride anion to the silicon atom of the tert-buthyldimethylsilane (TBDMS) group was responsible for the disruption of OSi bond, which generates an emissive species. UV–vis absorption, fluorescence steady state, and time resolved emission spectroscopy were employed. The lowest quantity of detectable amount of 3.3 μmol/L for F− was achieved for fluorescence measurements in acetonitrile solution. The system could be adapted to paper discs under a UV lamp (365 nm) for direct visual fluoride ion detection.