Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including epithelial ovarian cancer (EOC). Previously published data on gene methylation of EOC focused mainly on single gene or on cancer tissues. Objectives of the study were to estimate the promoter hypermethylation status of DAPK1 and p16 genes in circulating blood of EOC patients and to determine their association with clinicopathological features of EOC. This case-control study included 50 EOC patients and 20 apparently healthy and age matched female controls. Isolation of genomic DNA was carried out from peripheral venous blood. Methylation in promoter region of DAPK1 and p16 genes was determined by methylation-specific PCR. Methylation of DAPK1 was occurred in 42 out of 50 cases (84.0%) and methylation of p16 gene was occurred in 34 out of 50 cases (68.0%). Methylation of both genes was occurred in 25 cases (50.0%). Occurrence of methylation in DAPK1 and p16 genes was statistically significant (p < 0.0001) in cases compared to controls. Methylation of both genes was not statistically associated with age at diagnosis, menopausal status, histopathological types and FIGO staging of EOC. Identification of the peculiar promoter hypermethylation of DAPK1 and p16 genes might be a successful approach for ancillary diagnosis of EOC at early stage in blood sample.