Introduction: Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial regions. Although many new treatment strategies have been developed, the 5-year survival rate of patients has remained at approximately 55% for the past 30 years. One of the primary reasons for treatment failure is local recurrence. P53 is one of the most frequently mutated tumour suppressor genes in OSCC and is responsible for more than 50% of all relapses in patients with surgically treated oral carcinoma and clear margins. Ki-67 is one of the most common immunohistochemical markers used to study cell proliferation and was demonstrated to be "over expressed" in epithelial cells of premalignant and malignant oral lesions. The aim of the present study is to explore p53 protein and ki-67 expression in resected margins. Method: Immunohistochemistry was performed on 20 resected margins of OSCC biopsy specimens using p53 and ki-67 antibody kits. Result: Of the 20 resected OSCC specimen margins, were negative margins and 5 were positive margins. P53 and ki-67 were expressed as a nuclear stain in basal and suprabasal cells. Negative margins showed 86% and 60% of p53 and ki-67 expression respectively. Positive margins showed 40% and 80% of p53 and ki-67 expression respectively. Conclusion: p53 and ki-67 expression can show reactivity irrespective of grades of dysplastic epithelium. The expression of these molecules in the resected margins can be used as an indicator for poor prognosis, recurrence, and surgical boundary estimation as these markers indicate proliferation of the cells with abnormal DNA content. Keywords: p53, Ki-67, resected margins, OSCC, recurrence of OSCC