Cholesterol is an essential component of cell membrane. Abnormal cholesterol metabolism is not only closely related to cardiovascular diseases, but also closely related to the occurrence and progression of cancer. In the process of invasion and metastasis, cancer cells need a large amount of cholesterol to meet their rapid growth.Cholesterol is not metabolized into carbon dioxide and water and cannot be directly involved in energy supply. Cholesterol⁃derived metabolites participate in metabolic and immune regulation of tumor microenvironment in supporting cancer progression.To further promote tumor growth, intrinsic drivers in tumor cells or extrinsic factors in microenvironment can trigger changes in cholesterol metabolism during tumor progression. Furthermore, immune cells in the microenvironment also need cholesterol to maintain their normal functions.Simply lowering serum cholesterol may impair immune function and lead to tumor progression.The complex system of cholesterol regulation in microenvironment is formed by the grabbing of cholesterol by tumor cells and immune cells and the influence of cholesterol metabolites on each other. Therefore, to elucidate the characteristics of cholesterol metabolism in tumor cells and immune cells is the key to target cholesterol metabolism for cancer therapy. This review focuses on the effects of cholesterol metabolism changes on tumor cells and immune cells as well as the strategies of targeting cholesterol metabolism for cancer therapy. Combination therapy based on targeted cholesterol metabolism is expected to improve the efficacy of patients with certain characteristics of cholesterol metabolism.