Novel 1,3,5,7-tetrafluorocyclotetrasiloxanes were synthesized from cyclotetrasiloxanetetraol by a facile synthetic method. By adjusting the amount of the fluorinating reagent, synthesis of a single isomer of 1,3,5,7-tetrafluorocyclotetrasiloxanes as well as the preparation of all four isomers were accomplished. The products are expected to serve as potential precursors to not only well-defined silsesquioxanes but also asymmetric cyclic siloxanes.