Spontaneous splenic rupture (SSR) in a patient undergoing hemodialysis has been described as an extremely rare and potentially fatal complication. We report here spontaneous splenic rupture in a 52-year-old woman undergoing regular hemodialysis for end-stage renal disease (ESRD). She complained of colicky abdominal pain in the left upper quadrant area and dizziness when she assumed an upright posture. Her vital signs revealed low blood pressure and tachycardia, which was suggestive of hypovolemic shock. Abdomen CT scan showed splenic hematoma and hemoperitoneum. However, she had no history of any event triggering the splenic rupture. An exploratory laparotomy showed a ruptured spleen and an emergency splenectomy was performed. We suggest that spontaneous spleen rupture may be attributed to uremic coagulopathy and heparin-induced coagulopathy.