Titanium dioxide nanotube (TONT) arrays grown by electrochemical anodization were used as supports for alloyed PtNi catalysts which were developed by a cosputtering technique. The as-deposited PtNi on TONT had poor oxygen reduction reaction (ORR) activity with a significant overpotential, while the ORR activity of annealed PtNiTONT was improved. The maximum ORR activity, with a significant increase (120 mV) of the half-wave potential, was achieved for 400°C annealed PtNiTONT. This favorable enhancement was attributable to two factors. The first is the formation of a PtNi alloy catalyst, which resulted in the modification of the d -electronic structure of Pt, leading to the favorable adsorption of O2. The second factor is a strong metal-support interaction (SMSI) effect. When the high-temperature thermal treatment was conducted in the reducing gas (hydrogen gas) on the PtNiTONT, there was electron transfer from the reduced support to the Pt catalyst. This caused a change of the work function that altered the electronic properties of surface Pt atoms (X-ray photoemission spectroscopy measurement), leading to an enhancement of the ORR activity. To investigate the SMSI effect further, the thin PtTONT samples were prepared and used for the investigation of the interfacial region between the TONT support and the Pt catalyst.