Endometriosis is a benign gynecologic disease characterized by the implantation of functional endometrial tissue at ectopic positions, associated with an increased risk of malignant transformation. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns. Epigenetic disruption including DNA methylation and histone modification, resulting changes in gene expression capacity, are important in tumor progression and malignant cellular transformation, therefore, variation in genes involved in epigenetic mechanisms might lead to disease susceptibility. To evaluate this hypothesis, we investigated single nucleotide polymorphisms of epigenetic genes DNMT1, DNMT3B, HDAC1, SIRT1 and SIRT3 for association with endometriosis. Our study showed that the SNPs of these genes are significantly associated with endometriosis in South Indian women. The sequence variations within the epigenetic genes may have a possible aetiopathological role in the development of endometriosis.