MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by either translational inhibition or mRNA degradation. miRNAs play pivotal roles in physiological functioning and pathological progression. The function of microRNA-99a (miR-99a) in oral squamous cell carcinoma (OSCC) remains unclear. In the present study, we investigated the roles of miR-99a in OSCC development and the underlying mechanisms in 25 cases of primary OSCC tissues and Tca-8113 cells. The cells were analyzed using FACS analysis and western blotting. Results showed that the expression levels of miR-99a were markedly decreased in OSCC tissues compared with the adjacent non-tumor tissues (n=25). The results of in vitro experiments showed that miR-99a mimics significantly inhibited the proliferation of Tca-8113 cells, a tongue squamous carcinoma cell line, and that miR-99a mimics markedly induced the apoptosis of Tca-8113 cells. Furthermore, we demonstrated that mammalian target of rapamycin (mTOR) was directly targeted by miR-99a, as the overexpression of miR-99a in Tca-8113 cells downregulated the protein expression level of mTOR. Thus, our findings suggest that the downregulation of miR-99a in OSCC tissues is associated with tumor development. miR-99a regulates the growth and survival of OSCC cells and may be exploited as a biomarker and therapeutic target for patients with OSCC.