Abstract: Apolipoprotein A-Ⅰ (ApoA-Ⅰ), the predominant protein in plasma HDL, regulates cholesterol metabolism and exhibits anti-inflammatory and antioxidant functions. Multiple clinical studies suggest that serum ApoA-Ⅰ levels are associated with the occurrence, development, and prognosis of malignant tumors. Laboratory research also shows that ApoA-Ⅰ and ApoA-Ⅰ mimetics exert antitumor effects through antioxidation, immunoregulation, cholesterol metabolism, lysophosphatidic acid binding, and anti-angiogenesis. This paper reviews the role of ApoA-Ⅰ and ApoA-Ⅰ peptides in tumorigenesis and their potential value in diagnosis, treatment, and prognosis.