Purpose: In this study, we aimed to investigate the role of organochlorine pesticides (OCPs), in the development of thyroid tumors. Method: Seven derived OCPs measured by gas chromatography (GC), and enzyme activities of acetylcholinesterase (AChE), superoxide dismutase3 (SOD3), catalase (CAT), glutathione peroxidase3 (GPx3) and paraoxonase1 (PON1) and also malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC), and nitric oxide (NO), as oxidative stress (OS) biomarkers were assessed in the blood of 61 patients with papillary thyroid carcinoma (PTC), 70 patients with benign thyroid nodules (BTN), and 73 healthy individuals. Furthermore, all the studied enzymes were docked against the measured OCPs. Results: The results revealed that β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4-DDT, and 4,4-DDT levels along with MDA, NO and PC levels were elevated, while AChE, SOD3, GPx3, CAT, and PON1 activities and TAC levels were decreased in the PTC and BTN groups compared with the control group. Conclusion: The results of present study indicated that OCPs might play a major role in the development of thyroid tumors by disturbing the thyroid gland through several mechanisms including generation of OS. Importantly, in-silico analysis confirmed the in vivo findings.