Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are recognized as severe diseases of the lungs and are closely linked to cigarette smoking and environmental pollution and share common mechanisms such as oxidative stress, inflammation, matrix degradation, and airway remodeling. Epidermal growth factor receptor (EGFR), a transmembrane receptor featuring an extracellular ligand binding domain and an intracellular tyrosine kinase domain, has been recognized as a crucial player in these processes. EGFR is known to be dysregulated in both COPD and LC. In LC, oncogenic mutations that activate EGFR lead to an increased oncogenic response, positioning EGFR as a key regulator and hub for unregulated cell growth signaling. This signaling promotes tumor cell proliferation, invasion, migration, metastasis, and survival. Conversely, in COPD, dysregulated EGFR signaling in response to different stimuli results in heightened airway inflammation, remodeling, and mucus secretion, contributing to exacerbations of the disease. In this chapter, we explore the intricate connection and shared signaling pathways between COPD and LC, focusing on the EGFR cascade. We discuss how in both these conditions inflammation leads to altered EGFR signaling and examine various therapeutic strategies that can be implemented for better prognosis and treatment options in both conditions.