Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms in the world. Phase II enzymes such as glutathione S-transferases have been suggested to play an important role in protecting cells against damage induced by carcinogens, through regulation of the conjugation of a wide range of xenobiotics for excretion of hydrophilic metabolites. It was suggested that inactivated or down-regulated GSTP1 gene could increase genomic damage when individuals were exposed to carcinogens. The tumor suppressor gene P16INK4A is located on chromosome 9p21 and encodes the p16 protein, which binds selectively to CDK4 to inhibit activation of the CDK4/cyclin D complex in the G1 phase. p16INK4A is frequently down regulated by aberrant methylation of the 5'cytosine phosphoguanine island within the promotor region. Inactivation of these genes is involved in the initiation of tumors. This study was performed to evaluate the frequency of methylated GSTP1 and p16INK4A in the peripheral blood of HCC and liver cirrhosis patients and to evaluate its role as an early detector of HCC. This study was conducted on 10 HCC patients and 30 cirrhotic patients compared to 10 age and sex matched healthy volunteers representing the control group using methylation specific PCR (MSP). Methylation of GSTP1 was detected in 100% of HCC patients and 96.6% of cirrhotic patients; while p16INK4A was detected in 50% of HCC patients and 40% of cirrhotic patients. According to our findings, neither GSTP1 nor p16 methylation considered markers for early detection for HCC among liver cirrhosis patients as there was no significant difference in the frequency in methylation in HCC patients when compared to cirrhotic patients which may be referred to the small sample size.