Abstract: Recently, studies have demonstrated that several signaling pathways including Wnt, Notch, and Hedgehog which are involved in the regulation of the stem cells are abnormally activated in lung cancer. They are closely associated with some properties of the lung cancer stem cells, such as high tumorigenic, high metastasis, drug resistance and so on. In addition, several studies have shown that the population of the lung cancer stem cells, which are resistant to radiotherapy and chemotherapy significantly, highly express drug resistance proteins. Therefore, how to target lung cancer stem cells and ultimately cure the disease is becoming a hotspot in the cancer targeted therapy.