The medicinal plant Hypericum perforatum Linn, commonly known as St. John's wort, has been used as an antidepressant. To investigate whether St. John's wort possesses a protective effect against hydrogen peroxide (H 2 O 2 )-induced cytotoxicity in neuronal cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidino-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, flow cytometry analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with H 2 O 2 exhibited several apoptotic features, while those pre-treated with St. John's wort prior to H 2 O 2 exposure showed a decreased occurrence of apoptotic features. In addition, pre-treatment with St. John's wort inhibited H 2 O 2 -induced increase in caspase-3 enzyme activity. These results suggest that St. John's wort may exert a protective effect against H 2 O 2 -induced apoptosis in human neuroblastoma cells.