BACKGROUND: Currently, some studies have investigated the relationship between homocysteine (Hcy) levels and hypertension. However, within the population of individuals with hypertension, there is still a lack of relevant research data. Therefore, we utilized data from the National Health and Nutrition Examination Survey (NHANES) to explore the associations between Hcy levels and hypertension prevalence, all-cause mortality, and cardiovascular mortality, in order to understand the role of Hcy levels in the control, assessment, and treatment of hypertension. METHODS: In this study, the data utilized were derived from NHANES, which collected data from 1999 to 2006. A total of 7680 eligible participants were ultimately included. To explore the associations between Hcy levels and hypertension prevalence as well as blood pressure, a weighted multivariate linear regression model and restricted cubic splines were employed to adjust for confounding factors. Additionally, we conducted subgroup analyses to observe the associations between Hcy levels and hypertension prevalence, systolic blood pressure(SBP), and diastolic blood pressure (DBP) in different subgroups. Lastly, we employed Kaplan-Meier estimates and Cox proportional hazards regression models for survival analysis, elucidating the relationship between hyperhomocysteinemia (HHcy) and the risks of all-cause mortality and cardiovascular mortality among hypertensive patients. RESULTS: The average age of all participants was 44.82 years, with 51.8% being female. After adjusting for relevant covariates, a positive correlation between Hcy and the risk of hypertension was identified (OR=1.04, 95% CI: 1.02-1.07, P < 0.001). Multivariate linear regression results indicated a positive correlation between HHcy and blood pressure levels (SBP: β = 0.2, 95% CI: 0.10-0.30, P < 0.001; DBP: β = 0.09, 95% CI: 0.01-0.17, P < 0.05). Furthermore, restricted cubic spline(RCS) curve analysis revealed a nonlinear positive correlation between SBP and DBP with Hcy levels. Survival analysis results demonstrated that when blood Hcy concentrations exceeded 10 μmol/L, patients with hypertension experienced significantly increased all-cause and cardiovascular mortality rates (P < 0.001). CONCLUSION: Our research validates Hcy as an independent risk factor for hypertension, further confirming a nonlinear positive correlation between blood pressure and Hcy levels. HHcy was associated with small increases SBP and DBP proportional to the degree of homocysteine elevation. Additionally, HHcy was a high-risk factor for all-cause and cardiovascular mortality in hypertensive patients. This may provide new insights into the management and treatment of hypertension.