Notwithstanding RuO 2 is one of the most active catalysts toward oxygen evolution reaction (OER), a plethora of fundamental details on its catalytic properties are still elusive, severely limiting its large-scale deployment. Herein, spin-polarized Density Functional Theory Molecular Dynamics (DFT-MD) simulations, coupled with advanced enhanced sampling methods in the well-tempered metadynamics framework, are applied to gain a global understanding of RuO 2 aqueous interface (explicit water solvent) in catalyzing the OER, and hence possibly help in the design of novel catalysts in the context of photochemical water oxidation. The present study quantitatively assesses the free-energy barriers behind the OER at the (110)-RuO 2 catalyst surface revealing plausible pathways composing the reaction network of the O 2 evolution. In particular, OER is investigated at room temperature when such a surface is exposed to both gas-phase and liquid-phase water. Albeit a unique efficient pathway has been identified in the gas-phase OER, a surprisingly lowest-free-energy-requiring reaction route is possible when (110)-RuO 2 is in contact with explicit liquid water. By estimating the free-energy surfaces associated to these processes, we reveal a water-assisted OER mechanism which involves a crucial proton-transfer-step assisted by the local water environment. These findings pave the way toward the systematic usage of those techniques for the fine assessment of the activity of catalysts, considering finite-temperature and explicit-solvent effects.