Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and it has been steadily increasing in worldwide. Pituitary tumor transforming gene 1 (PTTG1) has been known as oncogene in a verity of cancers. Nevertheless, the expression and role of PTTG1 in OSCC progression remains largely unexplored. In this study, clinical datasets were analyzed to assess the genetic impact of PTTG1 on OSCC progression and to identify its functional roles in OSCC cell lines. We analyzed the expression of PTTG1 in head and neck squamous cell carcinoma (HNSC) and OSCC using databases form the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). To investigate the effect of PTTG1 on proliferation and migration abilities in OSCC cell lines, following the knockdown of PTTG1 in HSC-2 and SCC-9 cell lines, we analyzed the proliferation and metastatic abilities of OSCC cells using EdU and Boyden chamber assays. Our database analysis revealed that PTTG1 was significantly overexpressed in tumor tissues compared to normal tissues. Moreover, its expression correlated with clinical parameters of OSCC. In vitro experiments demonstrated that depletion of PTTG1 suppressed the ability of cell proliferation and migration in both HSC-2 and SCC-9 cell lines. In conclusion, our study suggests that PTTG1 may act as an oncogene in OSCC. These findings provide new insights into the mechanisms and clinical implications of PTTG1 expression in OSCC patients.