The mechanisms of the protective role of naringin on ox-LDL–mediated HUVEC injury were investigated by down-regulating YAP expression. HUVEC cells were divided into four groups: ox-LDL group, ox-LDL + naringin group, ox-LDL + naringin + shRNA-Con group, and ox-LDL + naringin + shRNA-YAP group. In each group, HUVECs were pretreated with naringin (100 µM) or naringin (100 µM) + shRNA-Con or naringin (100 µM) + shRNA-YAP, for 2 h, then exposed to ox-LDL (80 μg/ml) and incubated for 24 h. (A and B) Western blotting was performed to determine YAP protein levels. (C) Cell viability was determined using the CCK-8 assay. (D) LDH activity was quantified. (E) TUNEL-positive cells were quantified by TUNEL immunofluorescent staining. (F) Apoptotic cells were quantified with a FITC Annexin V apoptosis kit, via flow cytometry. Data are presented as mean ± SD, n = 6, ##P < 0.01 and ###P < 0.001 vs. the ox-LDL group, **P < 0.01 and ***P < 0.001 vs. the ox-LDL + naringin group.