Halloysite nanotubes (HNTs) is a promising support for liquid-phase hydrodeoxygenation (HDO) catalysts due to a wide abundance, low cost and tunable properties. Acid etching of halloysite by sulfuric acid was found to enlarge lumen diameter (24.3 nm), enhance specific surface area (154 m2/g) and acidity (0.343 mmol/g). Based on pristine and dealuminated HNTs, Ru-containing catalysts were synthesized via impregnation under microwave irradiation. The catalytic properties of synthesized catalysts in HDO of guaiacol were studied in batch reactors at 120–180 °C, under hydrogen pressure of 3 MPa, with guaiacol/Ru molar ratio of 200 in water as a solvent. Comparing the results of catalytic tests, we have concluded that the catalysts based on etched halloysite enhanced greater activity (TOF – 211 h−1) in the HDO of guaiacol compared their analogue supported on pristine HNTs. Moreover, the Ru-catalyst based on etched HNTs contributed to an increase selectivity to hydrogenolysis with effective oxygen removal.