The invention belongs to the technical field of spent fuel post-treatment, and particularly relates to a spent fuel post-treatment method based on a uranium cluster compound, which comprises the following steps: S1, disassembling and shearing a spent fuel assembly into small fuel rods; s2, dissolving the spent fuel by using hydrogen peroxide and an alkaline solution, and filtering to obtain a precipitate and a filtrate; s3, treating the filtrate obtained in the step S2 by utilizing gel electrophoresis, and separating to obtain a uranium cluster compound and a solution containing Pu, minor actinides and fission products; and S4, dilute nitric acid and hydrogen peroxide are added into the uranium cluster compound obtained in the step S3, uranium peroxide clusters are converted into hematite sediment, filtering is carried out, sediment is obtained, and separation of the uranium element is achieved. The spent fuel post-treatment process based on the uranium cluster compound has the advantages of being simple in process, small in corrosivity and the like, the risk of nuclear diffusion does not exist, and compared with a PUREX process, the spent fuel post-treatment process based on the uranium cluster compound has better economic benefits.