Breast cancer is the most common malignancy, which leads to both physical and psychological impairments.Accumulating evidence has suggested that negative mood is tightly related to initiation and progression of breast cancer.In this paper,we established a new animal model of breast cancer and chronic mild stress, and then evaluated the association between depression-like behaviors induced by chronic mild stress and breast cancer progression on the model of transgenic mice.The increasing tumor growth was largely attributable to depressive-like behaviors induced by chronic mild stress, presented as increased tumor incidence, enlarged tumor volume and relatively heavier tumor weight.Under phenomenon observed above, proteomics study using two-dimensional differential gel electrophoresis was applied to explore the involved protein changes.All these proteins were involved in breast cancer progression at varying stages.In addition, we searched the identified proteins and found that Thioredoxin 2 was the most potential marker linking depression-like behaviors with breast cancer development among the 8 candidate proteins.However, further functional studies will be conducted to confirm this finding, which may, in turn, pave a way for clinical treatment among breast cancer patients with chronic depression.