Essential hypertension (EH) is a chronic disease with clear epigenetic component. Inflammation and endothelial dysfunction have a great role in the development of persistent blood pressure elevation. The aim of this study was to explore an association between EH and DNA methylation in pro-inflammation cytokine gene interleukin-6 (IL-6) during the inflammatory process. We performed methylation analysis of peripheral blood DNA using bisulphite pyrosequencing technology between 96 EH patients and 96 age- and gender-matched healthy controls. The present results showed that three cytosine-phosphate-guanine (CpG) sites of IL-6 promoter CpG island had different lower methylation in EH group compared with controls, but only CpG2 (58.43 ± 7.53 versus 62.34 ± 9.65, P = 0.004) and CpG3 (51.52 ± 6.18 versus 57.45 ± 8.29, P<0.001) had statistical difference. Logistic regression analysis found CpG3 hypomethylation was a risk factor of EH (odds ratio = 1.111, adjusted P=0.004). In addition, we found hypermethylation of CpG1 (64.84 ± 7.06 versus 61.84 ± 8.61) and CpG2 (62.04 ± 7.40 versus 59.30 ± 9.57) in male compared with female. In male, we found hypomethylation of CpG2 (60.41 ± 7.74 versus 64.28 ± 6.36) and CpG3 (53.70 ± 8.62 versus 57.78 ± 7.87) of smoker versus non-smoker and hypomethylation of CpG2 (60.89 ± 7.32 versus 64.70 ± 7.03) and CpG3 (53.23 ± 7.99 versus 60.48 ± 7.58) of drinker versus non-drinker. Furthermore, the CpG2 and CpG3 had a negative correlation with systolic blood pressure and diastolic blood pressure (P<0.05). Receiver operating characteristic curve analysis showed that CpG2 (area under curve: 0.638, P = 0.001) and CpG3 (area under curve: 0.704, P<0.001) had a diagnostic value to predict the risk of EH. In summary, our study revealed hypomethylation of IL-6 was correlated with the risk of EH in the population assessed and we found the differences of IL-6 promoter methylation in gender, smoking and drinking.