The interactions and the protective effect of epigallocatechin gallate (EGCG) on human erythrocytes (RBC) and molecular models of its membrane were investigated. The latter consisted of bilayers built- up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. X-ray diffraction and differential scanning calorimetry experiments showed that EGCG induced significant structural and thermotropic perturbations in multilayers and vesicles of DMPC; however, these effects were not observed in DMPE. Fluorescence spectroscopy results revealed that EGCG produced alterations of the molecular dynamics at the level of the hydrophobic-hydrophilic interface in DMPC vesicles, and in isolated unsealed human erythrocyte membranes (IUM). EGCG also induced morphological alterations in RBC from their normal discoid form to echinocytes. These outcomes indicate that EGCG molecules were located in the outer monolayer of the erythrocyte membrane. The assessment of EGCG protective effect demonstrated that it inhibits the morphological alterations and lysis induced by HClO to human erythrocytes. The results obtained from this study suggest that the insertion of EGCG into the outer monolayer of the erythrocyte membrane might prevent the access and deleterious effects of oxidant molecules such as HClO and free radicals into the red cells, protecting them from oxidative damage.