Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck cancer. Few studies have analyzed the expression of proteins related to inflammation (COX-2) and tumor progression according to the histological grade of OSCC. Objective: Analyze the immunohistochemical expression of COX-2, Ki-67 (cell proliferation), Bcl-2/Bax (apoptosis), VEGF, and CD105 (angiogenesis) according to histological grades of OSCC. Material and methods: The immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF, and CD105 of 58 cases of OSCC was analyzed. 13 cases of oral mucosa (OM) were analyzed as controls. Results: COX-2, VEGF, CD105, and Ki-67 were higher in OSCC than in OM, particularly in poorly differentiated OSCC (p < 0.05). Bax expression was lower in poorly differentiated OSCC (p < 0.001). The Bcl-2/Bax ratio was higher in OSCC compared to MO (p < 0.05). Conclusion: There are immunohistochemical differences according to histological grades of OSCC, which could influence clinical behavior.