Objective To explore the role of forkhead box protein O3a (FOXO3a) in inhibiting the proliferation and metastasis of breast cancer cells by downregulation of vascular endothelial growth factorA (VEGF-A).Methods Cell proliferation bioassay and plate clone formation assay were used to compare the changes of proliferation after siRNA interference.Wound healing and Transwell were used to compare the changes of invasion metastasis after interference.Meanwhile,the changes of VEGF-A expression in the cells before and after interference were compared by real time polymerase chain reaction (RT-PCR) and Western blot.Furthermore,the expressions of mRNA FOXO3a and VEGF-A were detected in 20 cases of breast cancer patients in breast cancer tissues and adjacent normal breast tissues.Results The MCF-7 and MDA-MB-231 cells were increased in cell proliferation and invasion after interference.Further studies found that mRNA and protein expression of VEGF-A were up-regulated in MCF-7 and MDA-MB-231cells after interference.In vivo the expression of FOXO3a was lower in 15 cases of cancer compared to normal tissues,and the expression of VEGF-A was high in 15 cases of cancer (75％).FOXO3a and VEGF-A expression was highly negatively correlated.Conclusions This study showed that FOXO3a could inhibit the proliferation and invasion of breast cancer cells,which might be regulated by VEGF-A.It provides an important theoretical evidence for targeted inhibition of breast cancer metastasis.