Increasing evidence proposes the benefits of cisplatin-based chemotherapy in a subpopulation of patients with oral squamous cell carcinoma (OSCC), yet reliable indicators for this subpopulation are poorly explored. AURKA, also known as aurora kinase A, playing important functions in cell mitosis and making cells resistant to cisplatin through dysregulation of DNA damage repair networks, has been reported to be upregulated in OSCC, making AURKA a promising indicator. In this study, we recruited 78 patients with advanced OSCC to examine the expression of AURKA and the correlation with chemotherapy response and clinical outcomes. We found that AURKA was strongly expressed in 31 (39.74 %) of the 78 advanced OSCC samples and its expression was significantly associated with cisplatin resistance (P = 0.023), clinical recurrence (P = 0.021), and 5-year survival (P = 0.019). Chemotherapy increased AURKA expression in post-chemotherapy samples, yet with no significance (P = 0.101). Multivariate Cox proportional hazards regression model analysis demonstrated that lymph node samples with positive, strong AURKA staining, and poor chemotherapy response were independently associated with the 5-year survival and disease-free survival. Inhibiting AURKA expression in OSCC cell lines remarkably increased their sensitivity to cisplatin treatment by 2.5-fold difference. Our results imply that the overexpression of AURKA in advanced OSCC not only plays a role in the disease course but also shows an involvement in cisplatin treatment response. AURKA level may be a valuable predictor for patients with advanced OSCC, with downregulation of AURKA being a promising adjuvant therapy in this patient population.