Gene therapy has recently reached the front line in the treatments of different diseases. Although graphene oxide has been widely used as a gene vector, its clinical application is limited by its scarce inhomogeneity due to the different synthetic methods adopted for its synthesis. Recently, we have developed the preparation of a new classof graphene oxide, named oxo -G,obtained by a rigorous synthetic method with controlled size and surface chemistry. oxo-G has been successfully applied for the production of reduced graphene oxide with remarkable conductivity. Here, we applied oxo-G to gene delivery. After ad hoc functionalization, we found that oxo-G is able to efficiently complex siRNA and strongly induce gene silencing in vitro at 5 pg/cell doses, more than 1 order of magnitude lower than the best results reported in the literature using graphene-based materials. The aim of this work is to inspire the readers to develop further oxo-G materials for biomedical applications. We hope that oxo-G may be considered as an alternative candidate in future gene silencing use in vivo.