The Mg-Al-NO3 hydrotalcite (LDH) was pretreated in weak acid solution in order to improve the stability in acid environment. The pretreated LDH (pt-LDH) were loaded with the anticancer drug 5-fluorouracil (5-FU). The loading process followed the pseudo-first-order kinetics, where both film and intra-particle diffusions were participating in ruling the adsorption diffusion of 5-FU anions. The loaded pt-LDH hybrid (FU/pt-LDH) was characterized by XRD, EDS, FT-IR and TG/DSC, indicating that 5-FU anions were partially intercalated into the interlayer space in the pt-LDH by anion-exchange and the thermal stability of 5-FU in the FU/pt-LDH was enhanced. The release behavior of 5-FU from the FU/pt-LDH hybrid at pH 4.6 and 7.5 was studied. It was found that 5-FU was released faster at pH 4.6 than at pH 7.5, and the released amount was higher, where the acid stability of the pt-LDH carrier increased. The results showed that pt-LDH carrier was capable of slow and controlled release of 5-FU.