The catalytic selective hydrodeoxygenation of guaiacol to value-added cyclohexane is one of the sustainable biomass utilization pathways for which the Ru/HZSM-5 support catalyst has been considered as promising. However, the effect of the catalyst morphology on the catalytic properties must be further investigated. Four Ru catalysts with different support morphologies, two-dimensional nanosheets (Ru/HZSM-5-P), brick-shaped (Ru/ HZSM-5-G), cross-shaped (Ru/HZSM-5-J), and irregular particles (Ru/HZSM-5-D), were prepared by the impregnation method to investigate the effects of catalyst morphology and acidity on the conversion efficiency of lignin-derived guaiacol to cyclohexane. The catalytic activity data showed that Ru/HZSM-5-P exhibited the best catalytic performance among the four catalysts with a conversion rate of 99.9% for guaiacol and a yield of 99.9% for cyclohexane. The characterization results showed significant differences among the four catalysts in terms of accessibility (thickness and pore volume), acidity, metal particle size, and reduction temperature. The Ru/HZSM-5-P catalyst with a two-dimensional nanosheet structure showed the best accessibility, smaller metal particle size, reasonable metal−support interaction, and appropriate B/L. The relatively strong acid centers facilitate the activation of C−C and C−O bonds. Besides, the reduced Ru species on the Ru/ZSM-5 catalyst exhibited high H 2 adsorption activity, which was beneficial for the adsorption of guaiacol. This indicates that the difference in catalyst morphology could greatly affect its catalytic activity, thereby altering the conversion rate of reactants and selectivity of the products.