Neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) gene may play an important role in the development of hypertension by regulating the amiloride-sensitive epithelial sodium channel for sodium reabsorption. Recently, a functional polymorphism located at the last nucleotide of exon 1 (rs4149601) of the NEDD4L gene were found to be associated with hypertension both in African Americans and whites, and a "flip-flop" association with hypertension was found in two white samples for a polymorphism located at intron 13 (rs3865418). In this study, we aimed at examining the role of these two variants on essential hypertension in Chinese Hans. In a population-based association study, we observed significantly higher prevalence of T allelic frequencies (p = 0.023) in hypertensives than normotensives. In logistic regression analysis, the stronger association was found under the additive model with an odds ratio of 1.31 (1.04-1.67) for T allele (p = 0.025). The association remained significant (p = 0.039) with an odds ratio of 1.29 (1.01-3.66) when adjusting for age and sex. We also constructed an ANCOVA factorial model by using clinical parameters as the dependent variable for rs3865418 polymorphisms. A significantly higher diastolic blood pressure was observed at rs3865418 in the dominant model for the T allele (p = 0.009). The positive association still exist after controlling age and sex (p = 0.013). For rs4149601 polymorphism, however, we did not observe a positive association with hypertension by implicating either logistic regression models or ANCOVA models. Thus, our results support rs3865418 but not rs4149601 polymorphism of NEDD4L gene implicated in the prevalence of hypertension in Chinese Hans.