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Backgroud and purpose：6-shogaol is the major bioactive compounds present inZingiber officinale, and possesses the anti-atherosclerotic effect. Here,we evaluatedthe effects of 6-shogaol on oxLDL-induced human umbilical vein endothelialcells(HUVECs) injuries and its possible molecular mechanisms.Experimental approach： human umbilical vein endothelial cells(HUVECs) waspre-incubated with or without 6-Shogaol and stimulated by oxidized low densitylipoprotein (ox-LDL) in the presence or absence of LOX-1 siRNA or caspase-3inhibitor.Cell viability, cell apoptosis，cellular Reactive Oxygen species, NADPHoxidase and caspase-3, 8, 9 activities were measured.Key results：6-shogaol decreased the oxidation of LDL into oxLDL and attenuated theoxLDL-rcaused oxidative stress and cell damage. Exposure of HUVECs to 200 ug/mloxLDL induced masive cell apoptosis, however, 6-shogaol defended against suchinjuries. Application of Lox-1 small interference (si)RNA into HUVECs reduced thetranslation of this membrane receptor, and simultaneously increased 6-shogaolprotection from oxLDL-induced cell apoptosis. By comparison, overexpression ofLox-1 attenuated 6-shogaol protection. 6-shogaol inhibited oxLDL-induced Lox-1mRNA and protein expressions. Both 6-shogaol and Lox-1 siRNA decreasedactivities of caspases-9，-3, but not caspases-8. Pretreatment with caspase-3 inhibitorDEVD一CHO (25 umol/L) synergistically promoted 6-Shogaols protection againstcell apoptosis.Conclusions andimplications：this study shows that 6-shogaol can protect HUVECsfrom oxLDL-induced apoptotic insults via downregulating Lox-1-mediated activationof the caspase protease pathway.