Metal‐organic frameworks (MOFs) are novel porous materials that have been extensively used in sensors, catalysis, gas storage and separation, and drug deliver owing to their adjustable pore size, large surface area and high porosity. Among diverse MOFs, UiO‐66 can be a promising carrier for drug delivery due to high porosity and chemical stability. However, the adsorption mechanism of drugs in UiO‐66 has not been identified and need a further investigation. Hence, we utilized molecular dynamic (MD) simulation to investigate the adsorption mechanism of UiO‐66 as drug carriers. The MD simulation of UiO‐66 exhibits the busulfan loading of 80 %, ibuprofen of 20 % and 5‐fluorouracil of 30 %, respectively. We also demonstrated that the host‐guest interaction between UiO‐66 and drugs is dominated by the Van der Waals force. UiO‐66 shows the highest affinity for busulfan compared with ibuprofen and 5‐fluorouracil. In addition, it is certified the linear relation between the adsorption atoms and the interaction energy, which could help us to predict the interaction energy between drugs and UiO‐66 by the contact atoms.