ObjectiveTo explore the mechanism by which exosomes derived from gastric cancer cells MGC-803 promote tumor progression through the upregulation of ABCG8 expression. MethodsUltra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） lipidomics， quantitative real-time PCR （qPCR） and Western blot were used to verify the role of ABCG8 in gastric cancer progression. Exosomes derived from gastric cancer cells were introduced， and a series of in vitro experiments were conducted to evaluate their effect on ABCG8 expression， as well as on cell proliferation， migration， and clonogenic ability in normal gastric mucosal epithelial GES-1 cells. ResultsUPLC-MS/MS lipidomics analysis revealed significant changes in triacylglycerol （TG） among the differential lipids. qPCR and Western blot analysis showed that the mRNA and protein expression levels of ABCG8 in the GC-Exo-treated group were higher than those in the GES-1 cell group （P<0.05）. Colony formation and Transwell migration assays revealed that， compared with the GES-1 cell group， the GC-Exo-treated group exhibited a greater number of colonies （P<0.05） and migrated cells （P<0.05） after 48 h of treatment. CCK-8 assay results showed that the proliferation rate in the GC-Exo-treated group （50 μg/mL） was higher than that in the GES-1 cell group （P<0.001）. Lipidomics analysis revealed that， compared with the GES-1 cell group， TG levels were upregulated in the GC-Exo-treated group， accompanied by decreased levels of phosphatidylcholine （PC） PC（38：2e）. ConclusionExosomes derived from gastric cancer cells MGC-803 may promote tumor progression by upregulating ABCG8 expression to mediate cholesterol efflux， thereby triggering pro-carcinogenic lipid metabolic reprogramming in normal gastric mucosal epithelial cells.