C(sp3)–C(sp) bond formations are of immense interest in chemistry and material sciences. We report herein a convenient, radical-mediated and catalytic method for C(sp3)–C(sp) cross-coupling. Thus, with AgNO3 as the catalyst and K2S2O8 as the oxidant, various aliphatic carboxylic acids underwent decarboxylative alkynylation with commercially available ethynylbenziodoxolones in aqueous solution under mild conditions. This site-specific alkynylation is not only general and efficient but also functional group compatible. In addition, it exhibits remarkable chemo- and stereoselectivity.