Hidradenitis suppurativa (HS) is a chronic recurrent suppurative skin disease of unknown etiology, frequently involves axillae, inguinal area, buttock, and perineum, and is more frequent in women. Klinefelter syndrome, known as 47,XXY or XXY, is the set of symptoms that result from two or more X chromosomes in males. There have been reported many cases of autoimmune disease in patients with Kleinfelter syndrome, but no case has been reported with HS. We reported at a 30-year-old man with Klinefelter syndrome presenting suppurative nodules around the anus. We found that multiple purulent nodules with tenderness and odor was present around the anus and perineum, accompanied by scar and sinus on the periphery through physical examination. We diagnosed him as HS, based on clinical findings. When serum testosterone level was low (e.g, Klinefelter syndrome), level of tumor necrosis factor-α (TNF-α) was significantly increased. TNF-α is overexpressed in intact skin as well as lesions in patients with HS, which correlates with the severity of the disease. Although the exact mechanism is unknown, low male hormone level in Klinefelter syndrome associated with increased TNF-α, may have contributed to worsening the patient's disease. We reported that biologics were more effective than primary treatment such as antibiotics in patients with autoimmune or genetic diseases, which may be accompanied by increased TNF-α in patients with HS.