Abstract: Deoxyribonucleic acid (DNA) damage response (DDR) is one of crucial molecular mechanisms for homeostasis maintenance and tumor development. DNA topoisomerase Ⅱ binding protein 1 (TopBP1) plays a key role in maintaining genome stability and regulating DDR related signaling pathways. Recent studies have demonstrated TopBP1 promoted the growth, metastasis and drug resistance of cancer cells through various molecular mechanisms, and significantly correlated with cancer risk and clinical outcome. In this paper, the latest research progress of TopBP1 in breast and gynecological tumors, respiratory and digestive system tumors was reviewed, in order to further understand the mechanism of action of TopBP1 in different tumors, promote its transformation into clinical markers or drug intervention targets, and provide novel insights into the DDR based anti-cancer strategies.