The article reviews the role of APE1/REF-1, a protein with both endonuclease and redox activities, in cancer development. APE1/REF-1 is primarily involved in DNA repair through the base excision repair (BER) pathway, which addresses DNA damage caused by oxidation, alkylation, and single-strand breaks. Additionally, its redox domain regulates transcription factors such as AP-1, NF-κB, HIF-1α, and STAT3, which are crucial for cell growth, inflammation, and angiogenesis. Overexpression of APE1/REF-1 is associated with various aggressive tumor phenotypes and poor prognosis in human cancers. The protein's expression and activity are linked to processes like proliferation, invasion, inflammation, and resistance to cell death. Recent studies also highlight APE1/REF-1's role in controlling onco-miRNAs and RNA metabolism, suggesting that targeting this protein could be a promising therapeutic approach. The article emphasizes the importance of APE1/REF-1 in the hallmarks of cancer and its potential as a therapeutic target.The article reviews the role of APE1/REF-1, a protein with both endonuclease and redox activities, in cancer development. APE1/REF-1 is primarily involved in DNA repair through the base excision repair (BER) pathway, which addresses DNA damage caused by oxidation, alkylation, and single-strand breaks. Additionally, its redox domain regulates transcription factors such as AP-1, NF-κB, HIF-1α, and STAT3, which are crucial for cell growth, inflammation, and angiogenesis. Overexpression of APE1/REF-1 is associated with various aggressive tumor phenotypes and poor prognosis in human cancers. The protein's expression and activity are linked to processes like proliferation, invasion, inflammation, and resistance to cell death. Recent studies also highlight APE1/REF-1's role in controlling onco-miRNAs and RNA metabolism, suggesting that targeting this protein could be a promising therapeutic approach. The article emphasizes the importance of APE1/REF-1 in the hallmarks of cancer and its potential as a therapeutic target.