Gallic acid, a naturally occurring plant phenol with antioxidative activity, was found to induce cell death in promyelocytic leukemia HL-60RG cells, although many antioxidants are well known to protect the cell from oxidative stress. Morphological and biochemical studies indicated that the gallic acid-induced cell death is apoptosis. Flow cytometric analysis revealed that the apoptosis was not triggered at a specific phase of the cell cycle and that 2 h exposure of gallic acid to HL-60RG cells was enough to induce apoptosis. The inhibitory assay suggested that gallic acid-induced cell death was mediated by reactive oxygen species such as hydrogen peroxide, superoxide anion in addition to Ca2+ ion, calmodulin-dependent enzymes. Structure-activity analysis suggests that gallic acid induces apoptosis in HL-60RG cells, depending on its distinctive feature derived from the structure but not on its antioxidative activity.