The relationship between serum lung cancer markers and the air pollution remains unclear. To further reveal the correlation between air pollutants and lung cancer, a retrospective analysis of 446,032 asymptomatic healthy people and symptomatic healthy people from the Health Management Center of the First Affiliated Hospital of Chongqing Medical University from 2014 to 2019 was performed. The distribution characteristics of serum lung cancer markers, cancer embryo antigens (CEA), cytokeratin 19 fragment (CYFRA211), squamous cell carcinoma antigen (SCC), and nerve-specific enolase (NSE) was analyzed in these population. Two independent sample man-Whitney U test was used to analyze the correlation of lung cancer markers and age, and a Chi-square test was used to analyze the relationship between lung cancer markers and gender. The daily change trend was profiled for six main air quality indicators PM10, PM2.5, SO2, NO2, CO, O3 during the same period. The correlation between lung markers and air pollutants was investigated by Spearman and multiple linear regression. The results showed that CYFRA211 had the highest excess rate in the screening population. There were differences in the number of cases with concentrated expression of lung cancer markers in the different age groups. Among them, the people with NSE exceeding the standard were the youngest, and most of them were 40-55 years old. Besides SCC, the expression levels of other markers increased with age, and the expression levels of the four markers in males were significantly higher than those in females. Although the levels of PM10 and PM2.5 exceeded the WHO standard (World Health Organization. 2011), they were not correlated with lung cancer markers. Multiple comparisons showed that the air pollutants SO2 and CYFRA211, as well as NO2 and NSE were closely related, but there was no significant linear relationship between CEA, SCC, and air pollutants. In conclusion, among the four lung cancer markers, CYFRA211 had the highest abnormal excess rate in total screening population, and the expression levels of these markers varied by gender and age, with males showing significantly higher expression levels than females, and they increased significantly with age except for SCC. The differential expression of these lung cancer markers may provide more strategies for lung cancer screening in the corresponding population. Lung cancer markers, CYFRA211 and NSE, can be used as sensitive biomarkers for exposure to certain air pollutants and provide references for the prevention and management of air pollution.