Lung cancer has become one of the most prevalent cancers in the last several decades. Studies have documented that most cases of lung cancer are caused by inhaling environmental carcinogens while how external environmental factors lead to individual lung cancer is still an open issue as the pathogenesis may come from the combined action of multiple environmental factors, and such pathogenic mechanism may vary from region to region. Based on the data of lung cancer cases from hospitals at the county level in Henan from 2016 to 2020, we analyzed the response relationship between lung cancer incidence and physical ambient factors (air quality, meteorological conditions, soil vegetation) and socioeconomic factors (occupational environment, medical level, heating mode, smoking behavior). We used a Bayesian spatio-temporal interaction model to evaluate the relative risk of disease in different regions. The results showed that smoking was still the primary determinant of lung cancer, but the influence of air quality was increasing year by year, with meteorological conditions and occupational environment playing a synergistic role in this process. The high-risk areas were concentrated in the plains of East and Central Henan and the basin of South Henan, while the low-risk areas were concentrated in the hilly areas of North and West Henan, which were related to the topography of Henan. Our study provides a better understanding of the environmental determinants of lung cancer which will help refine existing prevention strategies and recognize the areas where actions are required to prevent environment and occupation related lung cancer.