A photo- and dioxygen-enabled intermolecular radical Csp3-Nsp2 cross-coupling between guanidines and perfluoroalkyl iodides has been developed. N2-Perfluoroalkacylguanidines, which are of biological importance, were obtained under mild conditions via Nsp2-perfluoroalkylation and subsequent hydrolysis. The role of dioxygen in the reaction system was tentatively elucidated; it was supposed to act as an electron shuttle (redox mediator).