Introduction NEDD4L is a candidate gene for hypertension on both functional and genetic grounds. The study is to investigate the relationships between the variation of NEDD4L and essential hypertension (EH) in Kazakh in China. Methods We screened the promoter and exons of NEDD4L in 94 Kazakh hypertensive individuals to identify representative variations. Then the representative variations were genotyped in a Kazakh general population, a case-control study was conducted. Results We did not identify any functional mutations in functional regions of NEDD4L. Three representative variations (296921-296923delTTG, rs2288774, rs2288775) were successfully genotyped in Kazakh population. The distribution of the dominant model (AA vs AG+GG) of rs2288775, the additive model and recessive model (II+ID vs DD) of 296921-296923delTTG differed significantly between case and control in female (p=0.040, p=0.024 and p=0.007 respectively). Logistic regression analysis showed that rs2288775 and 296921-296923delTTG were significantly associated with hypertension (rs2288775: OR=1.479, 95% CI 1.011 to 2.064, p=0.044; 296921-296923delTTG: OR=1.908, 95% CI 1.020 to 3.568, p=0.043) in female. The frequency of D-C-G haplotype was significantly higher for case than for control in female (p=0.020). Conclusions The genetic variations of NEDD4L may be associated with EH in female Kazakh.