Background and aims: Pesticides are nowadays known as one of the most important causes of human disorders worldwide. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in the development of lung cancer. Methods We determined the levels of seven derived OCP residues (α-HCH, β-HCH, γ-HCH, 2,4 DDT, 4,4 DDT, 2,4 DDE, and 4,4 DDE) and enzymatic antioxidant biomarkers including paraoxonase-1 (PON-1), erythrocyte's acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and non-enzymatic antioxidant biomarkers including total antioxidant capacity (TAC), protein carbonyl (PC), malondialdehyde (MDA), and nitric oxide (NO) in the blood samples of 51 lung cancer patients and 51 healthy subjects as controls. Furthermore, the effects of OPP exposure on the development of lung cancer and oxidative stress (OS) are indirectly assessed by measuring AChE and PON-1 enzyme activities. Results The average values of all the measured OCPs were significantly higher in lung cancer patients when compared with healthy control subjects. AChE, PON-1, GPx, and CAT activity levels as well as the amounts of PC, MDA, and NO were higher in patients with lung cancer than in the control subjects, while TAC values were lower in the patients. Moreover, our data showed a significant association between OCP concentrations and OS parameters. Conclusion The results suggest that OCPs and OPPs may have a role in lung cancer incidence in southeastern Iran, and at least one of the mechanisms by which OCPs and OPPs may contribute to increasing the development of lung cancer in the studied area is through OS generation.