Objective To explore the mechanism of ozone exposure-induced chronic rhinosinusitis by analyzing the alterations in the expression of oxidative stress-related genes in human nasal epithelium. Methods An in vitro cultured ozone exposure-induced human nasal epithelium model was established. The oxidative-stress-related genes of human nasal epithelium were detected by high-throughput polymerase chain reaction (PCR) chip before and after ozone exposure, and were verified by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of cyclooxygenase 2 (Cox2) and reactive oxide species (ROS) were detected by qRT-PCR, Western blotting and flow cytometry. Results A total of 84 oxidativestress-related genes were screened by PCR chip in the human nasal epithelium. It was found that the expression of aldo-keto reductase family 1 member C2 (AKR1C2), glutamate-cysteine ligase modifier subunit (GCLM), glutathione peroxidase 2 (GPX2), glutathione-disulfide reductase (GSR), heme oxygenase 1 (HMOX1), NADPH oxidase 5 (NOX5), prostaglandin-endoperoxide synthase 2 (PTGS2), superoxide dismutase 2 (SOD2), and serine peptidase inhibitor Kazal type 1 (SPINK1) was up-regulated after intensive ozone exposure, while the expression of C-C motif chemokine ligand 5 (CCL5), cytoglobin (CYGB), epoxide hydrolase 2 (EPHX2), glutathione S-transferase zeta 1 (GSTZ1), keratin 1 (KRT1), phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), myoglobin (MB), mitochondrial inner membrane protein MpV17 (MPV17), selenoprotein P (SEPP1), and trafficking protein particle complex 6A (TRAPPC6A) was down-regulated. At the same time, ozone exposure resulted in a large amount of ROS (fluorescence intensity of the exposure group and control group:184.3±6.8 vs 13.0±1.4, P<0.05) and increased expressions of Cox2 mRNA and protein (relative expression of mRNAs:6.4±1.2 vs 1.0±0.0, P<0.05; relative protein expression:11.7±2.6 vs 13.8±1.5, P<0.05). Conclusion After ozone exposure, GSTZ1, NOX5, SOD2 and other related genes are involved in the regulation of oxidative stress in nasal epithelium. The inflammatory response of nasal epithelium induced by ozone exposure may be related to the signaling pathways of Cox2 expression that regulated by these genes.