Abstract: Objective To observe the expression of kelch-like ECH-associated protein 1 (Keap1) and nuclear factor E2 related factors (Nrf2) protein in non-small cell lung cancer (NSCLC), and to explore its clinical association with NSCLC. Methods Keapl, Nrf2 protein expressions in 92 cases of NSCLC and its adjacent tissues(≥ 10 cm) were detected by immunohistochemical streptavidin-perosidase(SP) method and protein immunoblot method, and their correlation with NSCLC tumor tissue type, tumor-node-metastasis(TNM) stage, the degree of differentiation, lymph node metastasis were analyzed. Results The expression of Keapl protein and Nrf2 protein in NSCLC were increased by immunehistochemical staining. The protein optical density (OD) values of the adjacent tissues were (0.327±0.053) and (0.313±0.062) respectively, and two proteins in the NSCLC tissues were significantly elevated, and the lower the differentiation degree of NSCLC, the more obvious the increase of the two protein OD values. Moreover, the higher of NSCLC tumor T stage, the positive expression of Keap1 and Nrf2 protein increased. The expression of Nrf2 protein and Keapl protein in NSCLC tissues was elevated and correlated with the degree of differentiation of tumor tissues. Conclusions The high expression expression of Nrf2 protein and Keapl protein in NSCLC has some significance in judging the malignancy of tumor.