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Aim: This study examines the levels of CD24 and CD44 expression in premalignant oral lesions (PMOL) and locally advanced oral squamous cell carcinoma (OSCC) in order to improve the early detection of the disease. We utilized RT-PCR techniques to examine the expression of two cell membrane proteins, CD24 and CD44, in blood and tissue samples., Methods: A quantitative real-time polymerase chain reaction was performed to evaluate the expression patterns of CD24 and CD44 in blood and tissue samples obtained from individuals with PMOL ( n  = 20), OSCC ( n  = 20), and control subjects ( n  = 10). An independent t-test was utilized, revealing that CD24 demonstrated statistical significance with a p -value < 0.05. Fold change analysis had been performed to quantify the differences in expression between the two groups., Results: CD24 was found to be increased in both tissue and blood groups. CD44 expression was higher in the tissue group in contrast to the blood group. The results for CD24 were statistically significant, with a p -value < 0.05. The findings affirm the use of CD24 as a dependable biomarker for early detection and diagnosis of OSCC in both tissue and blood specimens., Conclusion: In conjunction with histological characteristics and clinicopathological factors, CD24 serves as a dependable biomarker for the early diagnosis of OSCC., (© The Association of Oral and Maxillofacial Surgeons of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)