The aim of this study was to determine the salivary concentrations of tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) in patients with premalignant and malignant lesions. The study involved 57 patients who were examined between 2008 and 2010 at the Department of Oral Medicine and Department of Oral and Maxillofacial Surgery of the Medical Faculty, University of Rijeka, Croatia. They were divided into three groups: 19 patients with oral premalignant lesions, 19 with oral squamous cell carcinoma and 19 healthy control volunteers. Whole saliva was collected and investigated for the presence of TNF-α and IL-6 by enzyme immunoassay at the Department of Dentistry and Maxillofacial Surgery, Medical Faculty, University of Graz, Austria. All groups had statistically significant differences in values of TNF-α and IL-6 (P < 0.001). The results suggest that these proinflammatory cytokines are elevated in the saliva of patients with oral squamous cell carcinoma and oral premalignant lesions as compared to controls, which may have diagnostic and/or prognostic significance.