Abstract: Objective : To study the expression and function of HOXA5 in breast cancer cells with different invasiveand metastatic potential and to gain insight into the underlying molecular mechanism. Methods : Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the differential expression of mRNA and protein of HOXA5. The entire open reading frame (ORF) of HOXA5 gene was amplifiedfrom MCF-10A cells by RT-PCR using the gene-specific primers and then were cloned into pcDNA3.1(+) andwere stably transfected into MDA-MB-231 breast cancer cells by LipofectamineTM 2000 TransfectionReagent. After selection in the presence of 1000μg/mL Geneticin (G418 sulfate; Invitrogen) for 4 weeks, thepcDNA3.1(+)-Rab27A positive and the empty vector positive colonies named as 231/Rab27A and 231/vectorwere identified by RT-PCR and Western blot analysis. Cell apoptosis was detected by flow cytometry (FCM)and Western blot was used to detect the expression of p53 and the activity of caspase 2 and caspase 8. Results : The expression of mRNA and protein of HOXA5 in breast cancer cells decreased with the increase ofthe invasive and metastatic ability. Overexpression of HOXA5 increased cell apoptosis by 7%-8% inMDA-MB-231 (P<0.01) and enhanced the activity of caspase 2 and caspase 8, but did not affect the expression of p53 in breast cancer cells. Conclusion : HOXA5 is negatively correlated with the invasive and metastatic ability of breast cancer cells and has effects on breast cancer cells through activating caspase 2 and caspase 8, thus promoting apoptosis.