We identified a set of hub genes (SLC22A18, CHAC1, ROBO4, TEK, NOTCH4, CD24, CD34, SOX2, PITX2, and GMDS) and common genes that establish a significant connection between COVID-19, smoking, and lung cancer.These genes can serve as biomarkers to detect early signs of lung cancer, especially in high-risk groups like smokers or individuals with COVID-19 history. This evidence concerns the gene NOTCH4 and COVID-19.