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Objective: To evaluate the effect and safety of clinical use of zoledronic acid in the treatment of malignant hypercalcemia. Methods: A multi-center, open phase Ⅱ clinical trial was conducted in 15 cases with malignant hypercalcemia who received zoledronic acid intravenously for 15 min. The level of blood calcium and side effects were recorded regularly within 28 days after injection. Results: One case was dropped out due to bad compliance. The complete response rate (the corrected serum calcium was reduced to normal level) was 100.00% (14/14). The medium time of complete response rate was 5.07 days. The medium maintain time was 22.30 days. Slight, or moderate fever was observed. Conclusion: Zoledronic acid can effectively reduce the malignant hypercalcemia. The use of zoledronic acid appears to be safety and convenient.