Objective: Hypoglycemia is most commonly caused by drugs for diabetes mellitus (DM), but other medical conditions including organ failures, sepsis, hormonal deficiencies, or cancers may result in hypoglycemia. In diabetic patients, old age, duration of diabetes, and polypharmacy are well-known risk factors for severe hypoglycemia. However, there have been limited reports on hypoglycemia in cancer patients. Methods: Sixty eight cancer patients with severe hypoglycemia among 92 patients who visited the emergency room (ER) of Chonnam National University Hwasun Hospital and treated with intravenous infusion of 50% dextrose from 2010 to 2011 were reviewed retrospectively. Results: The mean age of the subjects was 69.4 ± 11.7 years, and 50 (73.5%) were male. Initial mean blood glucose level at ER was 40.0 ± 23.3 mg/dL, and they needed 2.3 ± 1.9-times injection of 50% dextrose to recover from altered consciousness. The average time for recovery from hypoglycemia was 33.8 ± 138.7 minutes. Among the subjects, 47 patients (51%) had DM, and the duration of DM was 6.1 ± 8.1 years. The mean HbA1c was 6.8 ± 1.8% and antidiabetic regimens used in the patients included oral hypoglycemic agents in 30 (44.1%), insulin in 10 (14.7%) and both in 4 (5.9%). Lung cancer (12) was the most common cancer and other cancers associated with hypoglycemia were hepatocellular (11), pancreatic cancer (8), hematologic malignancies (8), gastric cancer (7), colon cancer (5) and others. Most common symptom on presentation was mental change followed by general weakness. Active malignancy itself was the most common etiology of hypoglycemia (38, 55.9%), and drugs used for DM were the second most common (21, 30.9%). 61 patients (89.7%) recovered from the hypoglycemia, but their in-hospital mortality rate was 33.8%. Conclusion: Active malignancy is the most common cause of severe hypoglycemia in oncology-based tertiary referral hospital, which is quite different from general hospitals, and the occurrence of hypoglycemia in cancer patients may herald the dismal prognosis.