The removal of crude oil from spent hydrodesulfurization catalysts constitutes the preliminary stage in the recovery process of valuable metals. However, the traditional roasting method for the removal exhibits massive limitations. In view of this, the present study used an ultrasound-assisted surfactant cleaning method to remove crude oil from spent hydrodesulfurization catalysts, which demonstrated effectiveness. Furthermore, the study investigated the mechanism governing the process with calculation and experiments, so as to provide a comprehensive understanding of the cleaning method’s efficacy. The surfactant selection was predicated on the performance in the IFT test, with SDBS and TX-100 finally being chosen. Subsequent calculations and analysis were then conducted to elucidate their frontier molecular orbitals, electrostatic potential, and polarity. It has been found that both SDBS and TX-100 possess the smallest LUMO-HOMO energy gap (ΔE), registering at 4.91 eV and 4.80 eV, respectively, and presenting the highest interfacial reactivity. The hydrophilic structure in the surfactant regulates the wettability of the oil-water interface, and the long-chain alkanes have excellent non-polar properties that promote the dissolution of crude oil. The ultrasonic-assisted process further improves the interface properties and enhances the oil removal effect. Surprisingly, the crude oil residue was reduced to 0.25% under optimal conditions. The final phase entailed the techno-economic evaluation of the entire process, revealing that, in comparison to the roasting method, this process saves $0.38 per kilogram of spent HDS catalyst, with the advantages of operational simplicity and emission-free. Generally, this study shed new light on the realization of efficient oil removal, with the salience of green, sustainable, and economical.