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The hydrothermal stability of NO oxidation is the key to the practical application of diesel oxidation catalysts in diesel engines, which in the laboratory requires that NO activity does not decrease after aging for 10 h with 10% H 2 O/air at 800 °C. On the one hand, the construction of a metal/oxide interface can lead to abundant oxygen vacancies (O v ), which compensate for the loss of activity caused by the aggregation of Pt particles after aging. On the other hand, YMn 2 O 5 (YMO) has excellent thermal stability and NO oxidation capacity. Therefore, a Pt/YMn 2 O 5 -La-Al 2 O 3 (Pt/YMO-LA) catalyst was prepared by the impregnation method. The support of the catalyst, YMn 2 O 5 -La-Al 2 O 3 (YMO-LA), was obtained by mixing high specific surface LA and YMO ball-milling. Under laboratory-simulated diesel exhaust flow, the NO oxidation performance of Pt/YMO-LA did not decrease after hydrothermal aging. Combining high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and oxygen temperature-programmed desorption (O 2 -TPD), the Pt/YMn 2 O 5 interface was formed after hydrothermal aging, and the increased O v can provide reactive oxygen to Pt and YMO. The cooperative catalysis of multiple active centers composed of Pt, YMO, and O v is the crucial factor to maintain the NO oxidation performance. In addition, in situ diffuse reflectance infrared Fourier transform spectra (DRIFTs) show that an increase in O v is beneficial to the adsorption and desorption of more nitrate and nitrite intermediates, thus achieving the hydrothermal stability of NO oxidation.