Background: The problems of optimizing the methods of diagnosis and predicting the course of lung cancer occupying a leading position in the structure of cancer are still relevant. Aims and Objectives: To establish the patterns of changes in the parameters of endogenous intoxication and lipid peroxidation processes in the saliva of patients with non-small-cell lung cancer (NSCLC) depending on the histological type of a tumor. Materials and Methods: A total of 505 people took part in the case-control study: The main group (NSCLC, n = 290) and the control one (healthy, n = 215). All participants were questioned and underwent the biochemical examination of saliva and histological verification of the diagnosis. The parameters of endogenous intoxication and lipid peroxidation were determined spectrophotometrically. Results: The results of the study support the hypothesis of association of endogenous intoxication and lipid peroxidation processes with the development of NSCLC. It was shown that against the background of NSCLC; the level of primary lipid peroxidation products decreases. Thereat, the content of triene conjugates and Schiff bases, as well as the MM 280/254 nm distribution coefficient, increases. The growth of these indicators with an increase in the size of the tumor was noted. The differences due to the histological type of NSCLC have been identified. Conclusion: Thus, with squamous cell NSCLC, a higher level of secondary lipid peroxidation products was noted. The presence of distant metastases in lungs significantly contributes to changes in indicators of endogenous intoxication and lipid peroxidation in case of adenocarcinoma.