Aims: Previous studies have demonstrated that tumor-stroma ratio (TSR) and tumor budding are of prognostic value for oral squamous cell carcinomas (OSCC). Herein we evaluated the prognostic significance of those histological parameters, individually and in combination, for OSCC.Methods: TSR and tumor budding (the presence of ≥ 5 buds at the invasive front) were estimated in 254 patients with OSCC. The clinicopathological association was investigated using a chi-square test, and the prognostic significance (cancer-specific survival and disease-free survival) was verified by Kaplan-Meier analysis and the Cox proportional hazard model.Results: TSR (≥ 50%, stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, whereas tumor budding significantly reduced cancer-specific survival. The TSR/tumor budding model was independently associated with a high-risk of cancer-mortality and recurrence (disease-free survival). In patients with early-stage tumors (clinical stage I and II, n=103), TSR, tumor budding and the TSR/tumor budding model were significantly associated with both cancer-related death and recurrence, while in advanced-stage tumors (clinical stage III and IV, n=144), only TSR and the TSR/tumor budding model were significantly associated with cancer-specific survival.Conclusions: TSR, tumor budding and their combination provide significant information on OSCC outcome, suggesting that their incorporation into the routine evaluation of histopathological specimens might be useful in the prognostication of OSCC patients.