The electronic and optical properties of the 5-fluorouracil (5-FU) on B12N12 surface were investigated theoretically by pure and time-dependent density functional theory (TD-DFT) calculations. Herein, the B12N12 nanocluster is utilized as a drug delivery vehicle for both the free and tautomeric forms of 5-FU drug. Our study indicates that the adsorption energy of 5-FU is an exothermic process with negative values of a few hundreds up to −1.779 eV, depending on their interaction configurations. The results show that the 5-FU drug is covalently bonded to the surface of its nitrogen head, whereas the other forms represent weak interactions due to noncovalent bonds between two species. The tautomeric forms of 5-FU and the free forms of the adsorbate show different behavior of binding energies and the changes in molecular energy gaps.