Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer related death.The tumor suppressor gene p16INK4A is located on chromosome9p21 and encodes the p16 protein, which binds selectively to CDK4 to inhibit activation of the CDK4/cyclin D complex in the G1 phase.Inactivation of this gene which normally inhibits progression to theG1 phase of the cell cycle is involved in the initiation of tumors. Several studies have shown that p16INK4A is frequentlydownregulated by aberrant methylation of the 5'cytosine phosphoguanineisland within the promotor region.This study was performed to evaluate the frequency of methylatedp16INK4A in the peripheral blood of HCC and liver cirrhosis patients andto evaluate its role as a risk factor for HCC using methylation specificPCR (MSP).Methylation of p16INK4A was detected in 6.7% (2/30) of HCCpatients and 5% (1/20) of LC patients.Results of the present study revealed that methylated p16INK4Acases in the HCC group had the highest AFP levels.Results of this study could not conclude hypermethylation ofp16INK4A as a risk factor for HCC.