Breast cancer is now the most frequently diagnosed cancer and is the sixth leading cause of cancer-related death in Chinese women. The regenerating islet-derived (REG) gene family encodes a group of proteins highly expressed in several human pathologies, many of which are associated with oncogenesis. REG3A gene has been previously reported to be up-regulated in liver cancers. However, REG3A expression in breast cancer has not been described. Therefore, we have used real-time fluorescence quantification (RT-PCR) to demonstrate REG3A expression in breast cancer and pericarcinomatous tissue. The results suggest the expression of REG3A is significantly reduced in breast cancer. The screening of human breast cancer with RT-PCR reveals REG3A gene is low expressed in MCF-7 cell line. Moreover, over-expressed of REG3A gene with entivirus can effectively repress the cell proliferation and the cell cycle was blocked in G0/G1 phase. Over-expressed REG3A gene can affect cell invasion and migration, which is confirmed by cell invasion and migration related genes using west blot (snail, ICAM, RhoC, MTA1, MMP-2 and MMP-9). In addition, JAK2/STAT3 signaling pathway, which is related with oncogenesis, is retained by using west blot. Characterization of the role of REG3A in the development of tumors should lead to a better understanding of the changes occurring at the molecular level during the development and progression of primary human breast cancer.