Herein, we describe a hexavalent tellurium-based chalcogen bonding catalysis platform capable of addressing reactivity and selectivity issues. This research demonstrates that hexavalent tellurium salts can serve as a class of highly active chalcogen bonding catalysts for the first time. The tellurium centers in these hexavalent catalysts have only one exposed interaction site, thus providing a favorable condition for the controlling of reaction selectivity. The advantages of these hexavalent tellurium catalysts were demonstrated by their remarkable catalytic activity in the cyanidation of difluorocyclopropenes through C-F bond activation, which otherwise were low reactive under the catalysis of strong Lewis acids or inaccessible by representative divalent/tetravalent tellurium-based donors. The catalytic activity of the hexavalent tellurium catalyst was further highlighted by its capability to address a previously unresolved reactivity problem associated with the strong Lewis acid approach, upon using some less reactive silyl enol ethers as nucleophiles in the functionalization of difluorocyclopropenes. The generality of this catalysis platform was demonstrated by its versatile application in different reaction systems. The hexavalent tellurium catalyst can differentiate two similar free OH groups in glycosyl acceptors to achieve excellent regio- and stereoselectivity in the synthesis of disaccharides, in which the tetravalent tellurium catalyst gave low reactivity and selectivity. Mechanistic investigation suggests that a catalyst-glycosyl donor-acceptor ternary supramolecular complex is operative.