Background/aims: Oral squamous cell carcinoma (OSCC) is the most common type of malignant neoplasm of the oral cavity and may become malignant from precancerous lesions such as oral lichen planus (OLP). This study aimed to determine the expression profile of miR-4789-5p, miR-3941, circ_0045638, and circ_0045639 to identify novel biomarkers for OSCC screening and prognostic predictors for the pre-malignant potential of OLP. Methods:  The expression levels of these miRNAs, circRNAs, and GRB2 target-gene in 30 OSCC and 10 OLP tissues compared to their adjacent-normal tissue samples were analyzed by qRT-PCR and compared clinicopathological characteristics in patients with OSCC. The potential diagnostic values of miRNAs and circRNAs in OSCC as risk factors of carcinogenesis were assessed by ROC curve analysis. Results: The expression levels of studied miRNAs and circRNAs were significantly lower in OSCC patients than in healthy controls (p < /em> < 0.001). Also, the expression of circ_0045638 and circ_0045639 were found significantly downregulated in OLP samples compared with healthy tissues but the expressions of miR-4789-5p, and miR-3941 were not significant (p < /em> = 0.078 and 0.074, respectively). Significant upregulation of the GRB2 gene was found in OSCC patients relative to adjacent-normal tissues (p < /em> < 0.001). We found a negative correlation between the expression miR-4789-5p, circ_0045638, and circ_0045639 and GRB2 in OSCC. Significant correlations were indicated between decreased expression of miR-4789-5p and perineural invasion, necrosis, and metastasis. The higher expression level of GRB2 was correlated with tumor size and lymphatic invasion. Area under the ROC curve (AUC) of miR-4789-5p, miR-3941, circ_0045638 and circ_0045639 were 0.971, 0. 821, 0.967 and 0.982, respectively, indicated their potential diagnostic value with excellent accuracy and specificity. Conclusion: miR-4789-5p, miR-3941, circ_0045638, and circ_0045639 expression status may provide the possibility to establish an accurate screening method for OLP that is a crucial step in the prevention of malignant transformation.