The hydrodeoxygenation (HDO) of bio-oil is considered among the most promising techniques for upgrading pyrolysis bio-oils to biofuels. However, its commercial application is challenging because of the complexity of the reaction. In particular, minimizing the hydrogen consumption in HDO is a main concern. In this study, ruthenium supported on mesoporous TiO2 (Ru/meso-TiO2) catalysts were prepared with various Fe loadings for this reaction, using anisole as a model substrate. Analytical techniques, such as transmission electron microscopy, CO chemisorption, and X-ray photoelectron spectroscopy, revealed that the addition of Fe increased the number of oxygen vacancies, reaching a maximum when the Fe loading was 1 wt.%. H-2 consumption can be reduced by performing HDO reaction at high temperatures. The Ru/meso-TiO2 without Fe converted anisole mainly to methoxycyclohexane, indicating that hydrogenation (HYD) is the dominant reaction pathway. The addition of Fe remarkably promotes the conversion and selectivity of the catalyst. The reaction path could be drastically changed from HYD to direct deoxygenation (DDO) by the addition of a proper amount of Fe. This change can be assigned to the synergism between Ru particles and Fe species on the surface of meso-TiO2 support. The catalyst with 1 wt.% Fe exhibited the highest conversion and benzene selectivity due to its largest number of oxygen vacancies, indicating that it utilized a minimum amount of H-2.