MicroRNAs (miRNAs) are small non-coding RNAs that function as regulators of gene expression. MiR-125 is a family of miRNAs that have been shown to be involved in various cancer types. In this study, for the first time, we showed that miR-125a-5p was specifically down-regulated in both colon cancer tissue and colon cancer cell lines. The tumor suppressor role of miR-125a-5p in colon cancer was supported by the observation that overexpression of miR-125a-5p inhibited cell proliferation and induced cell apoptosis in colon cancer cells. We also confirmed that in colon cancer cells, anti-apoptotic genes BCL2, BCL2L12 and Mcl-1 were direct targets of miR-125a-5p, and they were down-regulated by miR-125a-5p overexpression. Furthermore, restoration of BCL2, BCL2L12 and Mcl-1 expression in colon cancer cells could partially reverse the cell proliferation inhibition and apoptosis stimulation caused by miR-125a-5p overexpression, indicating that miR-125a-5p inhibits cell proliferation and induces apoptosis in colon cancer cells via targeting BCL2, BCL2L12 and Mcl-1.