Aim To investigate the levels of a disintegrin and metalloprotease 10 (ADAM-10) and soluble urokinase plasminogen activator receptor (suPAR) in the serum of hypertension patients with atherosclerosis and their relationship with the severity of disease. Methods From February 2021 to February 3,5 hypertension patients with atherosclerosis who visited our hospital were collected as the study group, and 76 healthy people were collected as control group. The patients in the study group were grouped into mild group (n＝40), moderate group (n＝42) and severe group (n＝43) according to the degree of atherosclerosis, after 60 days of treatment, the patients were grouped into a good prognosis group (n＝74) and a poor prognosis group (n＝51) based on their prognosis. Enzyme linked immunosorbent assay (ELISA) was applied to measure serum ADAM-10 and suPAR levels; Clinical data of patients with different prognosis were compared; Pearson method was applied to analyze the relationship between serum ADAM-10, suPAR levels and carotid intima-media thickness (IMT) in patients with hypertension and atherosclerosis; Multivariate Logistic regression was applied to analyze the influencing factors of poor prognosis in patients with hypertension and atherosclerosis; Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of ADAM-10 and suPAR alone and jointly for poor prognosis of hypertension with atherosclerosis. Results The levels of serum ADAM-10 and suPAR were significantly higher in the study group than those in control group (P＜0.05); The serum ADAM-10 and suPAR levels in moderate group and severe group were obviously higher than those in mild group (P＜0.05), while the serum ADAM-10 and suPAR levels were obviously higher in severe group than those in moderate group (P＜0.05); The serum ADAM-10 and suPAR levels, left and right IMT, systolic blood pressure, and diastolic blood pressure of patients with poor prognosis were significantly higher than those of patients with good prognosis (P＜0.05); Pearson correlation analysis showed that serum ADAM-10 and suPAR levels in patients with hypertension and atherosclerosis were positively correlated with systolic blood pressure, diastolic blood pressure and IMT (P＜0.001); Logistic regression analysis showed that the increased levels of systolic blood pressure, diastolic blood pressure, ADAM-10, suPAR and IMT were risk factors for poor prognosis of hypertension patients with atherosclerosis (P＜0.05); ROC curve analysis showed that the area under the curve (AUC) of serum ADAM-10 and suPAR levels alone and jointly predicting poor prognosis of hypertension with atherosclerosis was 0.9,0.830 and 0.900, respectively, the combination of the two was superior to their individual predictions (Z_combination-ADAM-10＝2.766, P＝0.006; Z_combination-suPAR＝2.602, P＝0.009).Conclusion The levels of serum ADAM-10 and suPAR in patients with hypertension and atherosclerosis are significantly increased, and are positively correlated with the severity of atherosclerosis. Both of them have a high predictive value for evaluating the prognosis of patients with hypertension and atherosclerosis.