The potential link between depression and cancer is an important unsolved question. To clarify this, we compared a cancer-related oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG), in peripheral leukocytes between 30 patients with depression and 60 age- and gender-matched healthy controls, and examined the 8-OH-dG-related factors. The degree of depression was assessed by the scores of the Center for Epidemiologic Studies Depression scale (CES-D) and the Profile of Mood States (POMS). The patients showed significantly higher 8-OH-dG levels than the controls. There was a significant positive correlation between the CES-D scores and the 8-OH-dG levels in depressive, particularly female, patients. Multiple regression analysis indicated that whether the subjects were patients or controls was a significant predictor of the 8-OH-dG levels in male and total subjects, as was the CES-D score or the Depression-Rejection score of the POMS in female subjects. This study suggests that clinical depression is a risk factor for cancer initiation in view of oxidative DNA damage.