Breast cancer (BC) is one hackneyed malignant tumor occurred on breast in female and possesses a higher mortality. Meis1 serves as a homeobox (HOX)-family transcription factor, and has been disclosed to take part into the modulation of diseases’ progression. However, the detailed impacts and associated regulatory pathway of Meis1 in BC progression keep dimness. The protein expressions were inspected through western blot. The cell viability and proliferation were determined through cell counting kit-8 (CCK-8) and colony formation assays. The cell apoptosis was determined through flow cytometry. The cellular morphological changes were verified through Phalloidin staining. The interaction between Meis1 and HOXB13 was confirmed through co-immunoprecipitation (Co-IP) assay. In this study, Meis1 expression was down-regulated in BRCA (breast invasive carcinoma) tissues from gene expression profiling interactive analysis (GEPIA) online database. And, it was uncovered that Meis1 existed the lower expression in BC cell lines. Besides, amplification of Meis1 restrained cell growth and aggrandized cell apoptosis in BC. Additionally, augmentation of Meis1 weakened epithelial-mesenchymal transition (EMT) process in BC through augmenting E-cadherin as well as declining neural cadherin (N-cadherin) and α-smooth muscle actin (α-SMA) expressions. Lastly, it was uncovered that overexpression of Meis1 retarded the HOXB13/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. To sum up, this study revealed that Meis1 restrained cell proliferation and epithelial-mesenchymal transition (EMT) process in BC through the HOXB13/PI3K/AKT signaling pathway. This work suggested that Meis1 may be one available molecular target for the amelioration of BC.