A process for the selective extraction and separation of vanadium and nickel from spent-residue oil hydrotreating catalysts by a direct acid leaching-solvent extraction method was studied. The extraction and separation of vanadium(IV) and nickel(II) are divided into two stages: acid coleaching of vanadium and nickel and solvent extraction. In the acid coleaching stage, the leaching ratios of vanadium and nickel reach 88.07% and 75.58%, respectively, which can realize highly effective coleaching. In the solvent extraction stage, countercurrent experiments show that the extraction ratio of vanadium can reach 99.21% after a three-stage extraction with P204 as the high-efficiency extractant of vanadium in the acidic environment, while nickel and iron are not extracted. After the anti-extraction solution is pretreated by aluminum precipitation, the extraction ratio of nickel reaches 99.79% after a three-stage extraction with LIX84-I as a high-efficiency extractant of nickel in ammonia medium. A process flow for the recovery of vanadium and nickel is proposed, which not only can realize the separation and recovery of vanadium and nickel but also can realize the recycling of reagents.