摘要Lung cancer is the leading cause of cancer-related deaths globally. In recent years, with the widespread use of genetic testing, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations. However, resistance to treatment is inevitable and eventually leads to tumor progression, recurrence, and reduction in the overall treatment efficacy. Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI-targeted therapy for lung adenocarcinoma. Lung cancer stem cells possess self-renewal, multilineage differentiation, and unlimited proliferation capabilities, which efficiently contribute to tumor formation and ultimately lead to tumor recurrence and metastasis. In this study, we evaluated the origin, markers, stemness index, relevant classic studies, resistance mechanisms, related signaling pathways, and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.