In this research, we focus our attention on the leaching peculiarity of uranium-containing Mg-Al layered double hydroxide (LDH) which is one kind of waste sediment in uranium tailings, generated by the alkalinization of uranyl raffinate. The effect of inorganic (CO32-, SO42-, PO43-) and organic (C2O42-, C6H6O72-, C6H16O24P62-) anions were investigated. Atomic force microscopy result showed that the thickness of CO32--LDH increased to 8.6 nm compared to original LDH whose thickness was 6.7 nm. Compared with the control sample (5.58 μm), the grain size with C6H16O24P62- anion grew to 7.04 μm. A large amount of CO32- can stay in LDH, up to 1.78 mol percent, while the C6H16O24P62- anion was only 0.41 mol percent. X-ray diffraction results showed that the anions could change the crystal structure of LDH, especially the C6H18O24P6 anion, and theoretical calculation also conformed this result. The leaching tests showed that the introduction of anions improved the leaching efficiency of UO22+ from LDH. The introduction of anions destroyed the super buffer property of LDH. Theoretical calculation results indicated that the anions could grab UO22+ and help the UO22+ escape from the LDH. This research gave guidance for long-term disposal of uranium-containing tailings.