As in all living cells, cancer cells are evaluating is very important in the frames of tumor development and treatment. As in all evolutionary process, the environment of living cells has an important role. Tumor cells have an environment is called tumor microenvironment, affects the therapeutic response and clinical results. Tumor microenvironments involve various cell types, extracellular matrix substances that are in the niche of cancer cells. The microenvironment is not only important in tumorigenesis but it is effective on therapeutic efficacy. In this review, we carried out the interaction between non-small cell lung cancer and its microenvironment to point out the significance of the tumor environment.