Cancer is a common type of noncommunicable disease, and its morbidity and mortality are rapidly increasing. It is expected to become the largest obstacle to the promotion of global human health in the future. Some transcription factors that play important regulatory roles in embryogenesis and subsequent tissue maintenance can be selectively amplified during tumorigenesis. Due to its high expression in the embryonic endoderm and mesoderm, GATA6 plays a crucial role in the normal development of early human heart, lung, digestive system, adrenal glands, breasts, ovaries, retina, skin and nervous system. Up to now, overexpression of the GATA6 gene has been shown to play an important role in several cancers, including lung cancer (LC), digestive system tumors, breast cancer (BC) and ovarian cancer (OC). However, the human body is a complex organism, which causes the transcription factor GATA6 to have multiple roles in cancer. In this review, we summarize the multiple roles of transcription factor GATA6 in various cancers and its regulatory mechanisms. The aim is to better understand the relationship between GATA6 gene expression and cancer development and to provide new insights for exploring potential therapeutic targets. This article is protected by copyright. All rights reserved.