Ruthenium (Ru)-based catalysts exhibited great potential for the alkaline hydrogen evolution reaction. However, the strong adsorption of H on the Ru surface and the undesirable agglomeration of Ru are obstacles to further boosting their hydrogen evolution reaction (HER) performance. Herein, we develop C60 fullerenol C60(OH)24 to stabilize, disperse, and activate Ru nanoparticles through Ru–O–C60 connections. Despite the ultrahigh Ru content (38.6 wt %), Ru nanoparticles are densely and uniformly dispersed on the C60 substrate due to the anchoring and confinement effects of C60 fullerenols. Moreover, the electron-withdrawing properties of C60 induce the electrons to flow from Ru to C60 through the Ru–O–C60 interface, which enhances the electronic metal–support interaction, thereby optimizing the adsorption behavior of different intermediates. The synthesized Ru–OC60-300 has a remarkably small overpotential (4.6 mV at 10 mA cm–2) and Tafel slope (24.7 mV dec–1), showing high activity and stability toward alkaline HER. Density functional theory simulations reveal that the Ru–O–C60 interface engineering weakens the Ru–H affinity, promotes water dissociation, and accelerates the hydrogen evolution kinetics.