Hexagonal boron nitride (h-BN) with a unique 2D architecture is a promising support for catalyst due to its large surface area, high thermal stability, and chemical inertness. However, the weak interaction between h-BN and active metal particles would lead to unexpected agglomeration or loss of active components. In this work, an oxygen-rich mesoporous boron nitride (BNO) support was synthesized by a two-step calcining process, on which Cu nanoparticles were dispersed via a typical adsorption−reduction procedure. The reduction of p-nitrophenol (4-NP) was successively carried out as a model reaction to determine the catalytic performance of the Cu/BNO catalyst. Excellent catalytic activity of 4-NP reduction was implemented with a reaction rate constant of 0.692 min −1 , which is maintained almost intact within five cycles. First-principles calculations suggest that the superior durability of Cu/BNO is largely attributed to the weakened conjugation effect of BNO upon O doping, which strengthens the interactions between Cu nanoparticles and BNO supports. Moreover, the doping O atom would significantly enrich the electron density of Cu, which is responsible for the superior activity toward 4-NP reduction.