For the synthesis of unsymmetrical acetylenes, a Sonogashira coupling-deprotection-Sonogashira coupling reaction sequence is often used. Removal of protecting groups requires harsh conditions or an excess of difficult to handle and expensive reagents. Herein, we disclose a novel catalytic method for the selective deprotection of trimethylsilylacetylenes in Sonogashira reaction. The reagent hexafluorosilicic acid, an inexpensive nontoxic compound, was used to promote the selective desilylation. This method enables the efficient synthesis of unsymmetric acetylenes with other silylated functional groups present. Further possibilities of the method were explored by synthesis of heterocycles.