Blastocystis hominisis an intestinal protozoan that is often neglected, despite causing abdominal pain and diarrhea. Previous research has demonstrated that lipids can be synthesized byB. hominisor can accumulate in growth medium, but their function and mechanisms in the pathogenesis ofBlastocystisremain unclear. Our study found that lipid-richBlastocystisST7-B can increase inflammation and disrupt Caco-2 cells more than the same parasite without the lipovenoes supplement. Additionally, the cysteine protease ofBlastocystis, a virulence factor, is upregulated and has higher activity in lipid-richBlastocystis. In order to better understand the effects of lipids onBlastocystispathogenesis, we treated lipid-lowering pravastatin duringBlastocystisST7-B culturing with a lipovenoes supplement, which decreased the lipid levels of theBlastocystisand reduced theBlastocystis-induced inflammation and cell disruption of Caco-2 cells. We also analyzed the fatty acid composition and possible synthesis pathway inBlastocystisST7-B, finding significantly higher ratios of arachidonic acid, oleic acid, and palmitic acid than in the other lipid components in lipid-richBlastocystisST7-B. These results suggest that lipids play a significant role in the pathogenesis ofBlastocystisand provide important information on the molecular mechanisms of and potential treatments forBlastocystisinfection.