Aim To study the diagnostic value of serum heparin-binding epidermal growth factor (HB-EGF) and serum amyloid A (SAA) in hypertensive patients with carotid atherosclerosis (CAS). Methods A total of 100 hypertensive patients were selected and divided into hypertension group (n＝42) and hypertension CAS group (n＝58); another 50 healthy subjects who underwent physical examination during the same period were selected as the healthy control group.The serum HB-EGF, SAA levels and CIMT in healthy control group, hypertension group and hypertension CAS group were compared. Pearson correlation analysis was used to test the correlation between serum HB-EGF, SAA levels and CIMT.Logistic regression analysis was used to analyze the risk factors of CAS. ROC curve was used to analyze the diagnostic value of serum HB-EGF and SAA levels for CAS in hypertensive patients. Results Compared with the healthy control group, the serum levels of HB-EGF and SAA in the hypertension group and the hypertension CAS group were significantly increased (P＜0.05), and the CIMT was significantly increased (P＜0.05). Compared with the hypertension group, the serum HB-EGF and SAA levels in the hypertension CAS group were significantly increased (P＜0.05), and the CIMT was significantly increased (P＜0.05). Pearson correlation analysis showed that serum HB-EGF and SAA levels were positively correlated with CIMT (r＝0.7,5%CI:0.7257～0.8662, P＜0.001; r＝0.5,5%CI:0.6688～0.8357, P＜0.001). Logistic regression analysis showed that high HB-EGF and high SAA were both risk factors for CAS in hypertensive patients (P＜0.05). The ROC curve showed that the optimal cut-off points of serum HB-EGF and SAA levels for diagnosing CAS were 19.84 μg/L and 8.97 mg/L, respectively. The AUC for diagnosing CAS alone and in combination were 0.1,0.810 and 0.875, respectively, the value of combined diagnosis of the two was higher than that of single diagnosis. Conclusion Serum HB-EGF and SAA levels were significantly increased in hypertensive CAS patients, and both were positively correlated with CIMT, which has high diagnostic efficacy for hypertensive CAS.