Oral squamous cell carcinoma (OSCC) forms the majority of the entire cancerous tumors which occur in the mouth. Current treatment advances, such as surgical resection, chemotherapy, and radiotherapy, have significantly helped reduce OSCC. However, the overall patient survival rate remains relatively low. MiRNAs, a non-coding RNA group, are essential for multiple biological functions, which are essential for the progression of cancer, including survival of the cell, migration, multiplication, differentiation, and apoptosis. The study aimed to explore the existing association between miR-487a-3p and PPM1A and elucidating their role in modulation of proliferation in OSCC cell lines. In this study, we used CAL-27 and TCA-8113 OSCC cell lines and human samples to validate our results. The manifestation of miR-487a-3p and PPM1A was checked using quantitative real-time PCR. The miR-487a-3p and PPM1A binding was investigated through western blot assay and dual-luciferase reporter gene. Functional experiments, including colony formation, CCK-8, and transwell experimentations, were undertaken to validate cells' growth and invasion activities. According to the results, the expression of miR-487a-3p is regulated in the OSCC cell lines compared to normal cells. Moreover, the mimicking of miR-487a-3p significantly reduces the OSCC cell growth and invasion, and PPM1A overexpression exerts oncogenic effects and hinders the anti-oncogenic effects of miR-487a-3p. In conclusion, the study demonstrated that miR-487a-3p might act as a tumor suppressor by inhibiting the growth and invasion of OSCC via regulating PPM1A expression.