Aims:Citrus lemonessential oil (CLEO) has been introduced as a strong antioxidant mixture. However, it is not efficient enough due to its hydrophobic nature. Nanoemulsions improve the drugs' bio-compatibility in aqueous conditions. Methods:The CLEO nanoemulsion (CLEO-NE) was formulated by ultrasound-based-emulsification and they were characterised. The anti-angiogenic and antioxidant activities were studied by the chicken chorioallantoic membrane (CAM) and antioxidant (ABTS and DPPH) assays, respectively. Finally, the apoptotic property of CLEO-NE on both HFF and A549 was evaluated by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and real time-PCR (measuring Cas-3 gene expression). Results:The 30.2-nm CLEO-NE droplets significantly increased Cas-3 in A549 cells and decreased angiogenesis in chick embryo chorioallantoic membrane (p < 0.01). Conclusion:In conclusion, CLEO-NE has the potential to be used as a safe cell-depended anticancer agent for human lung cancer. However, further genes and cell lines have to be studied to clarify its targeted-anticancer activity.