Non-alcoholic　fatty　liver　disease　(NAFLD),　characterized　by　hepatic　steatosis,　is　one　of　the　most　common　liver　diseases　worldwide.　So　far,　no　definitive　medical　treatment　has　been　established　to　treat　NAFLD　except　for　lifestyle　medication.　Nitzschia　laevis　extract　(NLE),　a　microalgal　extract　rich　in　fucoxanthin,　has　been　previously　demonstrated　to　reduce　bodyweight　in　high-fat-diet　(HFD)　C57BL/6J　mice,　indicating　potential　for　prevention　of　NAFLD.　In　the　present　study,　we　investigated　the　lipid-lowering　effects　of　NLE　in　HFD-induced　steatosis　murine　model　and　palmitate-treated　HepG2　cells.　The　results　showed　that　NLE　significantly　lowered　inguinal　fat　and　attenuated　hepatic　steatosis　in　C57BL/6J　mice.　Especially,　NLE　significantly　prevented　lipid　accumulation　in　HepG2　cells.　This　was　probably　due　to　its　capability　to　enhance　hepatic　mitochondrial　function　as　evidenced　by　the　increased　oxygen　consumption　rate　(OCR)　and　mitochondrial　membrane　potential　(MMP),　and　repress　fatty　acid　synthesis　through　phosphorylation　of　acetyl-CoA　carboxylase　(ACC).　Moreover,　fucoxanthin　was　identified　to　be　responsible　for　the　lipid-lowering　effect　of　NLE.　Taken　together,　NLE　or　other　microalgal　fucoxanthin-rich　products　are　promising　natural　products　that　may　help　prevent　against　NAFLD.