Gold nanoclusters were highly dispersed on hydrothermally prepared copper-ceria nanocatalysts and resulted in enhanced catalytic performance for preferential CO oxidation reaction, highlighting the direct interaction between Cu and Au through a Cu-Au interface. The presence of gold nanoclusters promoted the reducibility and oxygen mobility of ceria and copper-ceria catalysts, while a reduction pretreatment before gold deposition resulted in re-dispersion of copper species and further enrichment of ceria surface with these active species, thus enhanced interactions with atomically dispersed gold nanoclusters. The catalytic performance in preferential CO oxidation reaction depicted the promoting role of gold nanoclusters and reductive pretreatment in terms of activity, selectivity and CO2/H2O tolerance.