Abstract: Recent studies have discovered a selective autophagy—lipophagy, which can selectively identify and degrade lipids and plays an important role in regulating cellular lipid metabolism and maintaining intracellular lipid homeostasis. The process of lipophagy can be directly or indirectly regulated by genes, enzymes, transcriptional regulators and other factors. This review examines the role of lipophagy in reducing liver lipid content, regulating pancreatic lipid metabolism, and regulating adipose tissue differentiation, and summarizes the findings of the molecules (Rab GTPase, enzymes, ion channels, transcription factors, small molecular substances) involved in the regulation of lipophagy, which points to new directions for the treatment of diseases caused by lipid accumulation.