In-situ hydrodeoxygenation of a mixture of oxygenated compounds from bio-oil with hydrogen donor over supported multi-metal catalysts was investigated. As most previous in-situ hydrodeoxygenation reports focused on phenols, guaiacol, furfural, and acetic acid, this paper extends the scope to a mixture of oxygenated compounds of not only phenols, guaiacol, furfural and acetic acid, but also of lesser reported hydroxyl -propanone, cyclopentanone aiming at obtaining more liquid fuels. The method of incipient wetness impregnation was used to load the three metals (Zr, Ni, Ir) and Pd on the support of ZSM-5 and C, respectively. The conversion of acetic acid, hydroxyl -propanone, cyclopentanone, guaiacol, furfural, and phenol reached 99.7%, 99.3%, 100%, 100%, 100%, and 100%, respectively, including the total deoxygenation ratio of 99.6%, the liquid yield (96.5%), and the hydrocarbon yield (86.7%), under the suitable conditions. The sulfur content, the octane number, and the H/C ratio of bio-oil through in-situ hydrodeoxygenation have been improved, and reached 0, 89 and 1.9, respectively. We also speculated reaction pathways of different oxides according to the product distribution over ZrNi/Ir-ZSM-5 and Pd/C.