Objective:To gain insight into the mechanism by which sex-determining region of Y chromosome (SRY)-related high-mobility-group box 2 (SOX2) involved in carcinogenesis and cancer stem cells (CSCs).Data Sources:The data used in this review were mainly published in English from 2000 to present obtained from PubMed.The search terms were SOX2, cancer, tumor or CSCs.Study Selection:Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.Results:SOX2,a transcription factor that is the key in maintaining pluripotent properties of stem cells,is a member of SRy-related high-mobility group domain proteins.SOX2 participates in many biological processes,such as modulation of cell proliferation,regulation of cell death signaling,cell apoptosis,and most importantly,tumor formation and development.Although SOX2 has been implicated in the biology of various tumors and CSCs,the findings are highly controversial,and information regarding the underlying mechanism remains limited.Moreover,the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet.Conclusions:Here,we review the important biological functions of SOX2 in different tumors and CSCs,and the function of SOX2 signaling in the pathobiology ofneoplasia,such as Wnt/β-catenin signaling pathway,Hippo signaling pathway,Survivin signaling pathway,PI3K/Akt signaling pathway,and so on.Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.