In both in vitro and in vivo data, we demonstrated that long-term exposure to cigarette smoke extract (CSE) and its carcinogen polycyclic aromatic hydrocarbon benzo[α]pyrene (B[α]P) elevates IL-6 generation from lung cancer cells through the PI3K, Akt, and NF-κB signaling pathway, subsequently enhancing lung cancer migration and metastasis. The gene discussed is NFKB1; the disease is lung cancer.