Interactions between the polyamidoamine (PAMAM) dendrimer and drug molecules are of interest for their potential biomedical applications. The goal of this work is to examine the interaction of PAMAM-C12 25% dendrimer with morin. The ultraviolet-visible, fluorescence spectroscopic methods as well as molecular modeling were used to analyze drug-binding mode, binding constants and binding sites, etc. The experimental data showed that the binding constant of morin-PAMAM-C12 25% is about 10(5) L/mol. The interaction of morin with PAMAM-C12 25% is mainly driven by the hydrophobic, electrostatic, hydrogen bonds and van der Waals forces. There are mainly three classes of binding site of morin at the interface of PAMAM-C12 25%. These results provided some useful information for self-assembling and disassembling the PAMAM dendrimer as well as efficient drug delivery and therapeutic applications.