A hypercalcemic crisis (HC) is a life-threatening endocrine emergency if not promptly diagnosed and treated. Initial management for HC includes fluid resuscitation, diuresis, bisphosphonates, calcitonin, and glucocorticoids, along with diagnosing the underlying etiology of HC. However, for the refractory HC, continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) should be considered. We report a case of severe refractory HC successfully managed with CRRT using RCA and surgery. A 56-year-old female patient was admitted to University Medical Center Ho Chi Minh City due to a decrease in consciousness. Laboratory tests and clinical manifestations suggested the diagnosis of primary hyperparathyroidism. The patient was managed with strategies to lower calcium levels, including intravenous normal saline, oral fluid replacement via nasogastric tube, calcitonin, and bisphosphonate; however, the patient did not respond to the initial treatment. Subsequently, the patient underwent CRRT with RCA and calcium-free replacement fluid to reduce the calcium level before parathyroidectomy. The patient was discharged after 10 days of hospitalization. CRRT with RCA appears to be a potential, effective, and safe method for treating refractory hypercalcemic crises. Further research is required to investigate the role of CRRT with RCA in refractory hypercalcemia.