Aim To investigate the relationship between two functional polymorphisms: rs5718 at epithelial Na channel γsubunit (SCNN1G) gene and rs4149601 at neural precursor cell expressed developmentally down regulated 4-like (DEDD4L) gene and essential hypertension in Uyghur population. Methods A case-control study was performed in 344 hypertensive and 322 control subjects, which were randomly recruited from the rural area of Tulupan district. The body mass index (BMI) and waist hip ratio (WHR) was recorded. Fasting plasma glucose, triglyceride, and cholesterol were measured. The two polymorphisms were genotyped by Taqman technique. Results The essential hypertension and control groups were in Hardy-Weinberg equilibrium for both polymorphisms. The frequencies of GA, GG and A allele of rs5718 were 34.6%, 5.6% and 22.9% in hypertensives, respectively, which were 36.6%, 4.0% and 22.4% in controls. The frequencies of GA, GG and A allele of rs4149601 were 28.9%, 1.9% and 14.6% in hypertensives, which were 30.0%, 3.3% and 18.3% in controls, respectively. There were no significant differences of both genotype distribution and allele frequencies between hypertensive and control subjects in both polymorphisms, with or without adjusting for covariates age and gender in a logistic regression analysis. In further ANCOVA analysis, neither polymorphism was significantly associated with systolic blood pressure, diastolic blood pressure, BMI, WHR, glucose, triglyceride, and cholesterol levels. Conclusions Our observation did not support an association of the two functional polymorphisms (rs5718 and rs4149601) with essential hypertension in Uyghur population.