Aim: The objectives of the current study were to assess the level of miRNA‐16 expression in oral squamous cell carcinoma and its effect on cell apoptosis and proliferation following its suppression. Additionally, the study aimed to investigate the mechanisms that underlie the involvement of miRNA-16 and its target genes, Bcl-2 and, MAPK in the progression of OSCC. Materials and methods: The Oral Cavity Squamous Cell Carcinoma cell line (OECM-1) and Normal Human Tongue Fibroblasts (HOrF) were used in this in vitro study. The MTT assay was used to evaluate the cytotoxic effect following the cells' transfection with a miRNA-16 inhibitor. In both treated and untreated cells, the expression levels of the miRNA-16, Bcl-2, and MAPK genes were measured using SYBER green-based quantitative PCR. Tukey's multiple comparisons test and One-way analysis of variance (ANOVA) were used to analyze the data. Results: OECM-1 cells transfected with miRNA-16 inhibitor exhibited a significant increase in proliferation in comparison with the untreated and normal cells. Additionally, a significant increase in the expression of Bcl-2 and MAPK was associated with miRNA-16 inhibition compared to the untreated OECM-1 cells. Conclusion: The findings suggest that miRNA‐16 is a tumor suppressor miRNA that acts by cell proliferation inhibition and apoptosis induction in OSCC by directly targeting Bcl-2 and MAPK. This implies that miRNA‐16 could be a potential therapeutic target for OSCC.