In order to explore the primary diagnostic aspects of lung cancer the effects of radon on the genes methylation of p16 and MGMT in BALF cells and tumor markers in serum of rats were investigated. 30 male wistar rats were randomly and equally divided into 5 groups: control group, 30 working level month (WLM) group, 60 WLM group, 90 WLM group and 120 WLM group, respectively. The rats were exposed to multi-functional ecology radon cabinet except for control group. Methylation-specific PCR (MSP) was used to detect the methylation rates of p16 gene and MGMT gene in bronchoalveolar lavage fluid (BALF) cells, ELISA was used to test the concentration of lung cancer biomarkers in serum of rats. The results showed that the methylation rates of p16 gene and the level of CEA in 120 WLM group increased significantly compared to other groups (,P,<,0.05). The level of NSE in 120 WLM group was remarkably higher than that in other groups except for 90 WLM group (,P,<,0.05), but the methylation rate of MGMT gene and the concentration of CYFRA21-1 and p53 antibody did not change significantly among all the 5 groups (,P,>,0.05). The above results suggested that it might be benefit to screen biomarker of lung cancer induced by high concentration radon exposure as the methylation rates of p16 gene and the levels of CEA and NSE increased significantly in high dose radon exposed rats.