Low-density lipoprotein (LDL), a natural lipoprotein transporting cholesterol in the circulatory system, has been a possible drug carrier for targeted delivery. LDL can bind to the LDL receptor (LDLR) with its outside apolipoprotein B-100 and then enter the cell via LDLR-mediated endocytosis. This targeting function inspires researchers to modify LDL to deliver different therapeutic drugs. Drugs can be loaded in the surficial phospholipids, hydrophobic core, or apolipoprotein for the structure of LDL. In addition, LDL-like synthetic nanoparticles carrying therapeutic drugs are also under investigation for the scarcity of natural LDL. In addition to being a carrier, LDL can also be a targeting molecule, decorated to the surface of synthetic nanoparticles loaded with cytotoxic compounds. This review summarizes the properties of LDL and the different kinds of LDL-based delivery nanoparticles, their loading strategies, and the achievements of the recent anti-tumor advancement.