Using oxide supported atomically precise gold nanoclusters is an emerging field in heterogeneous catalysis. Such well-defined nanocatalysts represent a rather new model system enabling fundamental insights in catalytic reactions. In the present work, the stability of Au25 and Au144 clusters, supported either on TiO2 or SiO2, was examined upon thermal air pretreatment and, for the first time, upon liquid phase oxidation reaction. A pronounced influence of the support (TiO2 vs. SiO2) and cluster size (Au25 vs. Au144) was revealed by XAS, DRS and STEM. Upon pretreatment, Au144 was more stable which may be related to its specific cluster core structure and staple configuration. The catalytic properties in liquid phase cyclohexane oxidation were clearly size dependent, with Au144 yielding higher TOF values, particularly in the case of SiO2 supported catalysts. However, with respect to selectivity, TiO2 supported catalysts led to higher KA production than SiO2 supported ones. This can be explained by the different reaction pathways, as observed by in situ ATR. HERFD-XAS measurements of Au144/TiO2 catalysts revealed a pronounced cluster structure modification towards bulk gold during the reaction, in contrast to a high stability of Au144/SiO2. This study demonstrates the important role the support material has on the reactivity and stability of gold nanoclusters, which is key for their catalytic function.