Mice deficiency in regulator of G-protein signaling 2(RGS2) showed an evident hypertension phenotype. Here, we studied associations of genetic variations of RGS2 with essential hypertension in the Kazakh population. Two identified nonsynonymous mutations (K18N, Y178C) were not specific for hypertension. A significant association was observed between 1891-1892 TC insertion/deletion with hypertension in men (OR = 1.698, P = 0.03 ) and in total population (OR = 1.32, p = 0.044) in dominant model. The mean systolic blood pressure (SBP) of the ID+DD group was significantly higher than that of the II group (adjusted, p = 0.044). Our results suggest that D allele of 1891-1892 TC insertion/deletion of RGS2 might be an independent risk factor for hypertension in Xinjiang Kazakhs.