The aim of the study was to investigate the relationship between plasma levels of malondialdehyde (MDA), a routinely used marker of oxidative stress, and squamous cell carcinoma of the oral cavity and oropharynx (OSCC). The prospective cohort study comprised a total of 67 patients who underwent surgery for OSCC. MDA was assessed using high performance liquid chromatography. The MDA levels in the pooled T1-2 patients were lower than in the patients with T3-4 tumors. A negative correlation of MDA and tumor grade was shown. Seventeen patients who manifested recurrence during the 49.6 months follow-up had significantly increased MDA compared to those staying in complete remission. Kaplan-Meier analysis revealed that the median disease-free interval and overall survival in the group with MDA > median was 19.3 and 22.5 months respectively, in contrast to 31.5 and 31.6 months respectively, in patients with MDA < or = median. The prognostic value and low cost of MDA measurement could make it a versatile and useful prognostic tool for the identification of OSCC patients with a high risk of recurrence.