Hypothesis: Wettability effect has long been a concern in various aqueous lubrication systems including biological and industrial applications. The wettability may affect lubrication performance by changing interfacial viscosity or hydration force. The key point to reveal the mechanism is to design an ideal exper-imental system to exclude other bulk factors other than surface wettability. Experiments: In this work, silicon surfaces with different treatments were used to study the single factor effect of wettability on aqueous lubrication. The normal and friction forces of these surfaces were quan-tified by atomic force microscopy (AFM) in water environment. The interfacial viscosity was evaluated according to the probe dynamic approaching process. Macroscale and microscale lubrication experiments of other materials were also conducted as verification and supplement. Findings: A semi-quantitative relationship between friction and wettability was revealed and attributed to the competition between the attractive van der Waals interactions and wettability-dependent repul-sive hydration interaction, which determined the strength of the adhesive interaction and dominated the sliding energy dissipation. The contribution of viscous effect of water was considered to be relatively minor. The findings provide an in-depth understanding of aqueous lubrication and outline important guidelines for tuning adhesion and friction. CO 2021 Elsevier Inc. All rights reserved.