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Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC), is the most leading cause of cancer mortality throughout the world. Despite recent improvements in its treatment, it still remains a highly lethal disease. It is becoming increasingly clear that estrogen and estrogen receptors are involve in the pathogenesis and development of lung cancer. Estrogen receptor modulators and aromatase inhibitor may reverse the drug-resistance of platinum based chemotherapy in NSCLC patients and can enhance curative effect of epidermal growth factor receptor tyrosine kinase inhibitor. In this article the progress in the function of estrogen in NSCLC and the treatment based on the ER signaling pathways for NSCLC is reviewed.