Cerium oxide is a well-established catalytic material in industry. Recently, its ability to destroy toxic organophosphates (CWAs) was discovered. As the applications of cerium oxide in medicine are growing rapidly, there is an urgent need to examine possible interactions of cerium oxide with phosphorus-containing compounds playing a crucial role in living organisms. We have demonstrated that cerium oxide facilitate the cleavage of the phosphoester bonds in ATP and related compounds. The relations were established between the dephosphorylating activity of the nanocrystalline cerium oxide and its physico-chemical characteristics governed by the synthetic route. It was also shown that (nano)ceria promote the degradation of β-nicotinamide adenine dinucleotide (NAD), which implies that it may interact with some more complex biologically relevant molecules.Recently, cerium oxide has been used in many exciting applications in biology and medicine, where its enzyme-mimetic abilities can be exploited. A more in-depth understanding of its interactions with biologically relevant molecules is highly desirable. It is shown in this study that certain forms of cerium oxide, namely the nanocrystalline cerium oxide (nanoceria) prepared by the thermal decomposition of cerium carbonate, may exhibit a remarkable ability to promote the dephosphorylating reactions of nucleotides and related compounds -adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine monophosphate (IMP), cytidine monophosphate (CMP), guanosine monophosphate (GMP), thiamine pyrophosphate (TPP) and thiamine monophosphate (TMP). The dephosphorylation proceeded under relatively mild (ambient) conditions with a rate constant proportional to the concentration of nanoceria and was almost independent of pH. The phosphoester bonds were cleaved through nucleophilic substitution, utilizing the surface hydroxyl groups as nucleophilic agents, whereas the electrophilicity of the phosphorus atoms was enhanced by the Lewis acid effect of the cerium cations. Moreover, more complex biologically relevant molecules may be subject to degradation in the presence of cerium oxide, namely β-nicotinamide adenine dinucleotide (NAD). The key characteristics of cerium oxide (surface area, crystallinity) as well as its surface chemistry and dephosphorylating activity are governed by the calcination temperature -the most effective cerium oxides were prepared by annealing at temperatures below ca. 600°C. Notably, certain commercially available cerium oxides exhibited even higher dephosphorylating activity than the in-house nanoceria.