Objective. Oxidative stress and imbalance in the oxidant/antioxidant system have a critical role in carcinogenesis by affecting necrosis and apoptosis. The aim of this study is to evaluate the oxidant/antioxidant status and cell death modes in patients with oral squamous cell carcinoma (OSCC). Materials and methods. Twenty-nine patients with OSCC and 29 control subjects were included in the study. The levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP) and ferric reducing antioxidant power (FRAP) were determined in plasma samples of all subjects. The necrotic and apoptotic cell death modes were evaluated with M65 ELISA and M30 ELISA, respectively. Results. MDA and AOPP values as oxidative stress markers were higher in patients with OSCC than in the control group. FRAP values evaluating plasma antioxidant status increased in OSCC patients. M65 and M30 levels indicating necrosis and apoptosis were significantly higher in OSCC patients compared to controls. There were significant correlations between MDA, AOPP and FRAP; M65 and M30 values. Conclusions. The elevated levels of oxidative stress markers together with the increase of antioxidant capacity and the presence of a strong correlation between MDA, AOPP and FRAP suggest an activation of antioxidant defense against accentuated oxidative stress determined in OSCC. Enhanced oxidation of lipids and proteins may cause decomposition of cell membranes with subsequent leakage of cytoskeletal cytokeratins as CK18 and caspase-cleaved CK18 (evaluated as M65 and M30, respectively) in the circulation, suggesting that both cell death modes are affected in OSCC.