Objective: To investigate the expressions of transforming growth factor α (TGF-α) and epidermal growth factor receptor (EGFR) in the parathyroid gland tissue of patients with secondary hyperparathyroidism (SHPT) and their significance. Methods: The tissue specimens of parathyroid gland tissue from 36 SHPT patients and 7 healthy subjects were collected. The parathyroid gland tissues with diffuse hyperplasia or nodular hyperplasia were distinguished by HE staining, the protein expressions of TGF-α, EGFR and Ki-67 in all the parathyroid gland tissues were determined by immunohistochemical staining, and the relations of TGF-α and EGFR expressions with the clinicopathologic factors of SHPT patients were analyzed. Results: Of the 36 SHPT patients, the parathyroid gland presented diffuse hyperplasia in 17 cases and nodular hyperplasia in 19 cases. The types of hyperplasia showed no significant relation with the clinicopathologic factors that included age, gender, dialysis time, preoperative parathyroid hormone level, blood levels of calcium and phosphate, calcium-phosphate product, albumin, hemoglobin, blood urea nitrogen, creatinine and alkaline phosphatase of the patients (all P>0.05). All expressions of TGF-α, EGFR and Ki-67 were significantly elevated in an increasing order in normal, diffuse and nodular hyperplastic parathyroid gland tissue (all P<0.05). Conclusion: TGF-α and EGFR expressions are increased in the parathyroid gland tissue of SHPT patients, and are closely related with the type of the hyperplasia of the parathyroid of SHPT patients.