ABSTRACT: The TNM staging system for oral squamous cell carcinoma (OSCC) provides clinicians a dependable foundation for patient prognosis and management decisions, but in clinical practice, treatment outcomes of patients with OSCC are sometimes unsatisfactory. This retrospective study investigated the association between survival and clinicopathological characteristics and histological grades of 2535 patients with OSCC. Additionally, the present study aimed to compare the predictive abilities of histological grades with other common prognostic factors. The enrolled patients were divided into three groups by two experienced pathologists into well-differentiated, moderately differentiated, and poorly differentiated groups, according to the WHO classification. Finally, we designed an observational, retrospective study based on the histological grading of tumors to compare their clinicopathological characteristics and conducted survival analysis among the three groups. Advanced tumor stage was diagnosed in 23.9%, 44.0%, and 55.1% of patients with grades 1-3 OSCC, respectively. By T status, T3 or T4 tumors were found in approximately 22%, 34%, and 40% of patients with grades 1-3 OSCC, respectively. By N status, lymph node metastases were found in 6.1%, 29.3%, and 45.9% of patients with grades 1-3 OSCC, respectively. Thus, significant survival differences were observed based on different OSCC histological grades. Meanwhile, in the multivariate (adjusted) analysis, N1 and N2 stages, extranodal spread, and poor differentiation were associated with a higher recurrence risk than the other common prognostic factors. In conclusion, 5% of patients in our study presented with poorly differentiated OSCC at diagnosis. Furthermore, grade 3 OSCC has worse prognosis and is more aggressive than grades 1 and 2 OSCC. In the future, we should focus on modifying individual therapy for poorly differentiated OSCC to achieve improved outcomes.