Denosumab, a human monoclonal antibody to the receptor activator of nuclear factor-κB ligand, is a novel therapy to osteoporotic fracture and skeletal-related events in patients with bone metastases. Hypocalcemia is its known adverse effect, although it is generally mild and transient and usually occurs in patients with severe chronic kidney disease or end-stage renal disease. We reported a case 61-year-old woman who received a single dose of denosumab and developed severe symptomatic hypocalcemia associated with prolong QTc interval requiring hospitalization for intravenous calcium.