Background and aim: microRNAs are a group of small non-coding single-stranded RNAs that control post-transcriptional gene expression. They can act as oncogenes or tumor suppressors by amplifying or preventing the expression of certain genes. present study was conducted to assess the expression of miRNA-3651 in paraffin blocks of oral squamous cell carcinoma (OSCC) cells using qRT-PCR method in Islamic Azad university, dental branch of Tehran in 1399.Material and methods: This case-control study was conducted on 20 paraffin blocks of irritation fibroma (IF) as control group and 20 paraffin blocks of patients with oral squamous cell carcinoma as case group. After RNA extraction, qRT-PCR was performed. all experiments were repeated 3 times for each sample. Eventually the data were analyzed by SPSS 24 statistics software. Differences in miRNA expression levels between the two groups were compared using the independent samples t-test. In order to evaluate the correlation between mean levels of miRNA-3651 marker and different variables (grade, age and sex of patients), Kruskal-Wallis test, Pearson's correlation coefficient test and independent samples t-test were used, respectively.Results: The results showed that the mean expression of this biomarker method was 10.15± 5.44 rpm in normal tissue and 8.11± 1.57 rpm in cancerous tissue. Despite the lower expression of miRNA-3651 in cancerous tissue samples than normal samples, this decrease was not statistically significant (P> 0.05). There was no significant difference between the mean level of miRNA-3651 marker and different grades, age and sex of patients (p> 0.05).Conclusion: In the end, it seems that the evaluation of changes in the expression of miRNAs such as miRNA-3651, can be a minimally invasive method, in early detection and screening of patients with OSCC. Decreased expression of miRNA-3651 marker in cancerous tissue compared to normal tissue indicates the importance of these biomarkers, including miRNA-3651 in the diagnosis of oral cancer, and the researchers of this project suggest further and broader investigations on the mechanism of action and signaling cascades associated with this marker in oral cancer.