Objective To investigate the risk factors and prevention measures of hypocalcemia and hypoparathyroidism (HPP) after thyroidectomy. Methods Clinical data of 449 patients with thyroid diseases, who received thyroidectomies in the Department of Thyroid and Breast Surgery of Changhai Hospital of Second Military Medical University from Jan.1 to Jun.30, 2016 were retrospectively analyzed, including 95 males and 354 females, with an average age of (48.99±12.81) years old. The risk factors of post-operative hypocalcemia or HPP were screened by smooth curve fitting, threshold effect analysis, one-way ANOVA analysis and multivariate analysis using the EmpowerStats and R software. Results Among the 449 patients, 27 cases (6.01%) developed lower parathyroid hormone (PTH), 43 (9.58%) developed hypocalcemia, and 23 (5.12%) developed transient HPP, of which one patient might develop permanent HPP. The risk of post-operative hypocalcemia was increased by 4% for every 1% decrease in post-operative PTH (P<0.000 1). Patients with thyroid carcinoma had the highest risk of HPP, followed by nodular goiter and hyperthyroidism. There was significant difference in the incidence of HPP among patients with six thyroid diseases(P<0.05). The larger of surgical resection range, the higher the incidence of HPP. Bilateral total/subtotal thyroidectomy plus central lymph node dissection in central area was a risk factor of the post-operative HPP (P<0.05). Conclusion The thyroid pathological type, surgical method and difficulty are important factors influencing the parathyroid function after thyroidectomy. Post-operative change of PTH levels has an important role in predicting the incidence of HPP and hypocalcemia.