Endothelial lipase (LIPG) plays a critical role in lipoprotein metabolism, cytokine expression, and the lipid composition of cells. Thus far, the extensive investigations of LIPG have focused on its mechanisms and involvement in metabolic syndromes such as atherosclerosis. However, recent developments have found that LIPG plays a role in cancer. This review summarizes the field of LIPG study. We focus on the role of LIPG in lipid metabolism and the inflammatory response, and highlight the recent insights in its involvement in tumor progression. Finally, we discuss potential therapeutic strategies for targeting LIPG in cancer, and the therapeutic potential of LIPG as a drug target.