Guaiacol, a phenol derived compound produced by the thermal degradation of lignin, was selected as a model compound to study the catalytic hydrodeoxygenation (HDO) process for upgrading pyrolysis bio-oils. Guaiacol is among the major components of bio-oils; however, it is thermally unstable which leads to catalyst deactivation. In the present study, four noble metal catalysts (Pt, Pd, Rh, and Ru) supported on activated carbon were tested in a fixed-bed reactor at atmospheric pressure and their performance for the guaiacol HDO process was measured. Our results showed that, among the tested catalysts, Pt has higher deoxygenation activity and shows little deactivation for 5 h. Additionally, the operating temperature for the Pt catalyst was optimized and found to be 300 degrees C. Finally, results from catalyst characterization demonstrated that polyaromatic deposits, especially the condensed ring compounds, are the most likely cause for catalyst deactivation.