Objective To explore the therapeutic effect of microwave ablation plus parathyroidectomy in primary hyperparathyroidism (PHPT) with hypercalcium crisis. Methods Eleven patients with primary hyperparathyroidism with hypercalcemia who did not respond to medical treatment and had contraindications to emergency surgery were enrolled. After the diagnosis of hypercalcemia crisis, the patients were ineffective in medical treatment within 48 hours, and emergency microwave ablation of the parathyroid adenoma was performed, and the parathyroid adenoma was resected after the clinical symptoms disappeared and the serum calcium dropped to the normal range. The changes of parathyroid hormone and serum calcium and phosphorus levels after microwave ablation of parathyroid adenoma were analyzed, and the optimal timing of surgery after the laboratory test results were reduced to normal, and the effects of microwave ablation and sequential surgery on the clinical symptoms, calcium and phosphorus laboratory results were investigated. Results Six hours after thermal ablation of the parathyroid gland, the serum parathyroid hormone levels of the patients decreased significantly. The pre-ablation serum calcium level was (3.49±0.16 mmol/L), which decreased to (2.39±0.63 mmol/L) after thermal ablation. The serum calcium level decreased to the safe range and stabilized within two days. One day after surgery, the serum parathyroid hormone and calcium levels decreased, and the phosphorus level increased significantly compared with before surgery (P<0.01). Low calcium levels occurred in 5 patients (45.5%) within 2 days after surgery, but were restored to normal after calcium supplementation via oral and intravenous administration. Heart rate decreased significantly, and the mental and joint symptoms, bone pain, and gastrointestinal symptoms such as nausea and vomiting improved significantly within one week after surgery. Conclusion Microwave ablation sequential to surgery is a novel, safe and effective method in treating primary hyperparathyroidism with hypercalcemia. In the clinical treatment of patients with primary hyperparathyroidism with hypercalcemia and contraindications to emergency surgery, microwave ablation is first used to inactivate parathyroid adenoma, which can significantly reduce the level of calcium and parathyroid hormone, and create conditions for surgery. Sequential surgery is significant in improving symptoms and reducing parathyroid hormone levels.