Aim To investigate the risk factors of depression in patients with hypertension. Methods 110 patients with hypertension combined with depression and 110 patients with hypertension alone were enrolled in this study,and the general data and serum factor levels of the two groups of patients were collected and compared. Multivariate Logistic regression analysis was performed on the variables with statistical significance in univariate analysis. Results Univariate analysis showed that cortisol(Cor)and renin precursor(Rep)levels were significantly increased and heme oxygenase-1(HO-1)levels were significantly decreased in patients with hypertension combined with depression (P＜0.05), but there was no significant differences in other indicators between the two groups. Multivariate Logistic regression analysis was used to analyze the three variables selected by univariate analysis. It was found that HO-1 (OR=0.2,5%CI:0.001~0.251, P＜0.01) and Rep(OR=5.9,5%CI:3.054~11.706, P＜0.001) were the important risk factors of depression for patients with hypertension. Conclusion Low HO-1 level and high Rep level are the important risk factors of depression for patients with hypertension.