The transcription factor family activator protein 2 (TFAP2) is vital for regulating both embryonic and oncogenic development. The TFAP2 family consists of five DNA-binding proteins, including TFAP2A, TFAP2B, TFAP2C, TFAP2D and TFAP2E. The importance of TFAP2 in tumor biology is becoming more widely recognized. While TFAP2D is not well studied, here, we mainly focus on the other four TFAP2 members. As a transcription factor, TFAP2 regulates the downstream targets directly by binding to their regulatory region. In addition, the regulation of downstream targets by epigenetic modification, posttranslational regulation, and interaction with noncoding RNA have also been identified. According to the pathways in which the downstream targets are involved in, the regulatory effects of TFAP2 on tumorigenesis are generally summarized as follows: stemness and EMT, interaction between TFAP2 and tumor microenvironment, cell cycle and DNA damage repair, ER- and ERBB2-related signaling pathway, ferroptosis and therapeutic response. Moreover, the factors that affect TFAP2 expression in oncogenesis are also summarized. Here, we review and discuss the most recent studies on TFAP2 and its effects on carcinogenesis and regulatory mechanisms.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-023-04189-1.