Lung cancer is the leading cause of cancer death worldwide. Cancer metastasis and resistance to treatment (including radiotherapy, chemotherapy and targeted therapy) are two major causes for the poor survival of lung cancer patients. Epithelial-mesenchymal transition (EMT) is involved in cancer cell invasion, resistance to apoptosis and stem cell features. The process of EMT is controlled by a group of transcriptional factors, zinc finger proteins and basic helix-loop-helix factors. Signaling pathways activated by intrinsic or extrinsic stimuli converge on these transcriptional factors and regulated the phenotypic changes of cancer cells. These EMT regulators may play an important role in cancer progression. In lung cancer, Slug is the most thoroughly investigated EMT regulator. The expression of Slug is associated with lung cancer invasion and resistance to target therapy. In this review, we focus on the current understanding of the role of Slug in the carcinogenesis and progression of lung cancer.