Aim To investigate whether the onion essential oil from Allium cepa has a protective effect on the oxidative damage cell model of atherosclerosis (As) and whether the protective mechanism is related to the regulation of janus kinase/signal transduction and transcriptional activator (JAK/STAT) pathway and NF-кB pathway. Methods Volatile oil extracting equipment was used to extract the essential oil from fresh Allium cepa. GC-MS was used to analyze the liposoluble components of the essential oil from Allium cepa. MTT method was used to detect the effect of the essential oil at different concentration and time on the cell proliferation of human umbilical vein endothelial cell (HUVEC). The HUVEC damage model has been established by using 80 mg/L oxidized low density lipoprotein (ox-LDL) to HUEVC for 24 h. The cell was stained by oil red O. The total cholesterol (TC) was detected by commercial kits. Free cholesterol (FC)/TC was more than or equal to 50%, which indicated whether HUVEC damage has been formed. ELISA kit, reactive oxygen species (ROS) kit and superoxide dismutase (SOD) kit were used to study the onion essential oil of anti-atherosclerosis effect and mechanism in vitro. Results 9.9008 g essential oil was extracted from 26615.5 g fresh Allium cepa, and the average yield of essential oil was 0.372‰. GC-MS analysis showed that the total relative content of organic sulfide in the essential oil was 47.64%, among which the content of 2-thiazolidinethione among the organic sulfide compounds was the highest (12.52%), followed by 1,3,5-trithiane (4.42%) and diallyldisulphide (3.82%). The cell proliferation was the best after 200 mg/L onion essential oil had acted on HUEVC for 6 h. HUEVC was induced by 80 mg/L ox-LDL for 24 h, the cells had a large number of red dye particles and FC/TC was not less than 50% of HUVEC cells which showed lipid accumulation and cholesterol and triglyceride metabolism has caused HUVEC damage. The onion essential oil significantly reduced HUVEC damage model secretion of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) (P<0.01) and the produce of ROS, promoted the produce of anti-inflammatory factor IL-10 (P<0.01) and increased activity of intracellular SOD (P<0.05). Conclusion The onion essential oil produced in this study has protective effect on the HUVEC damage model induced by ox-LDL.