Oral premalignant lesions represent the most prevalent lesions observed within the oral cavity. These lesions generally remain asymptomatic until they advance to more severe stages, at which point their progression to oral squamous cell carcinoma (OSCC) becomes evident. Addressing this transformation necessitates further investigative efforts. The PTEN (phosphatase and tensin homolog) gene functions as a crucial tumor suppressor, with its expression regulated by a variety of complex mechanisms, including transcriptional, post-transcriptional, and post-translational processes. MicroRNAs (miRNAs) are significant modulators of PTEN expression and play an integral role in the transition from oral premalignant lesions to OSCC. This review evaluates the impact of miRNA dysregulation on PTEN and examines the continuum model of tumor suppression. It posits that the loss of PTEN functionality may transpire without alterations to the DNA sequence, particularly through mechanisms associated with miRNA regulation. Furthermore, this discourse elucidates the structural interactions between PTEN and miRNAs, particularly in the context of oral premalignant lesions, which may influence the rate of transformation to OSCC. Such insights are crucial for informing treatment strategies. The review also explores the potential of targeting specific miRNAs to restore PTEN functionality, intending to improve clinical outcomes for patients diagnosed with OSCC. By elucidating these regulatory interactions, this analysis aims to identify pathways conducive to the development of targeted therapeutic strategies.