Purpose of the Study: The present study was conducted to evaluate epigenetic alteration of five tumour suppressor genes in the oral precancer and cancer patients. Materials and Methods:The study was carried out in three groups namely control group of five people (normal healthy individuals), 10 oral leukoplakia patients and 10 oral squamous cell carcinoma patients. Incisional biopsy was done and part of the tissue sent for histological examination and part of tissue sent for hypermethylation study of p16, p15, hMLH, MGMT, E-cadherin tumour suppressor genes. Methylation specific polymerase chain reaction was carried out for detecting methylation in promoter regions of tumour suppressor genes. The resultant PCR products were run in a 2.5% agarose gel and the promoter hypermethylation status of the five tumour suppressor genes were analysed. Results:In oral Leukoplakia patients, 60% of methylation in the case of p16 gene, 30% of methylation in the case of MGMT gene and 60% of methylation in the case of E-cadherin gene. In oral Squamous cell carcinoma patients, 60% of methylation in the case of p16 gene, 40% of methylation in the case of MGMT, 60% of methylation in the case of E-cadherin gene, 20% in case of p15,10% in case of hMLH gene. Conclusion:Our results suggest that epigenetic mechanisms of inactivation of tumour suppressor genes, such as aberrant methylation of p16 and E-cadherin genes occur early in head and neck tumourigenesis and might play a role in the progression of these lesions.