Heme oxygenase was regarded as a regulator of oxidative stress, which was believed to underlie the etiology of hypertension. To assess the effect of its encoded genes (HMOX1 and HMOX2) on hypertension, we designed a case-control study in 503 cases and 490 controls. The results indicated that the rs9607267 of the HMOX1 gene was significantly associated with essential hypertension (EH) and the Hap3(T-C-G) of the HMOX1 gene was also significantly associated with the risk of EH. No association was observed between the HMOX2 gene and EH. The multifactor-dimensionality reduction analyses results did not show any interaction between the HMOX1 and HMOX2 genes underlying the development of hypertension.