Effective recovery of elements from spent catalysts can not only avoid environmental hazards, but also alleviate the pressure of resource scarcity. This study proposes a hydrometallurgical process for the selective recovery of MoO3 and NiO from the spent hydrofining catalysts. First, valuable metals were leached with 0.5 mol/L H2SO4 and 4 wt% H2O2 at 25 °C for 20 min, resulting in the dissolution efficiencies of Mo, Ni and Al were 95.6%, 96.5% and 13.8%, respectively. Then, bis-(2-ethylhexy)phosphinic acid (P227) was chosen as the Mo extractant due to its higher separation factors of βMo/Al and βMo/Fe compared to di-2-ethylhexylphosphoric acid (P204) and 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (P507). Extraction efficiency of 99.9% Mo was achieved at pH of 0.5 with 0.3 mol/L P227, whereas only 0.061 g/L Fe and <1 mg/L of other impurity elements were co-extracted. The complete stripping of Mo was realized with 0.4 mol/L (NH4)2CO3. Subsequently, a synergistic extraction system bis(2,4,4-trimethylpentyl)dithiophosphinic acid (Cyanex 301) and trioctylphosphine oxide (TOPO) was employed to extract Ni, where the extraction efficiency was more than 99.9%. Around 99.9% of Ni was stripped with 9 mol/L HCl. With the addition of TOPO, not only the extraction ability of Ni was improved, but also realized the complete stripping of Ni. The two oxides MoO3 and NiO were prepared from the stripping solution. In addition, the extraction mechanism of Mo and Ni was studied. The total recovery efficiencies of Mo and Ni were 94.1% and 93.1%, with the purity of 99.9% and 99.0%, indicating that this innovative process can be utilized to recover MoO3 and NiO from the spent hydrofining catalysts.