Abstract: The occurrence and development of carcinoma depend on a number of factors and multiple genetic changes and is a multi-step process. Besides cancer tissue itself, the hypoxia, low glucose, low amino acids and low PH value of the cancer microenvironments were also interacted with cancer, these cancer microenvironments resulted in stress response, including stabilization of hypoxia-inducible factors (HIFs), induction of the unfolded protein response (UPR) and activation of the AMP-activated protein kinase (AMPK) pathway, which was also involved in cancer progression, angiogenesis, invasion, metastasis and therapeutic resistance. Activating transcription factor 4 (ATF4) belongs to the activator of transcription family (ATF) with the basic region leucine zipper (b ZIP) that is involved in protein-protein interactions.ATF4 plays important role in regulating the survival, growth and development of normal tissue, and involved in autophagy, redox and apoptosis. The recent study shows that the expression of ATF4 increase in various cancer tissues, especially in cancer microenvironment (region lacking of nutrients), suggesting that ATF4 in cancer microenvironment is involved in the maintenance of cancer metabolism, the survival of cancer cell in the lack of nutrition, and is related with cancer progression and drugs resistance. This paper mainly summarizes about the sources and role of ATF4 in cancer cell growth and development and in cancer biology, and its mechanism in cancer progression and drug resistance, the paper also prospects the role of ATF4 related cancer treatment, and provide ideas for anti-cancer research targeting the ATF4 pathway.