Herein, we report the first facile Cu-free click reaction between alkynyl sulfonium and azide at ambient temperatures in aqueous media. DFT computations indicate that the sulfonium group is the key factor to gaining reactivity by stabilizing LUMO+1 and influencing the charge distribution of the triple bond. Sulfonium alkynes can be easily synthesized and scaled up, and most of them are biocompatible. We prepared candidate molecules and tested their use in multiple proof-of-concept biological applications.