Colorectal cancer (CRC) remains a major cause of carcinoma-related deaths worldwide. MicroRNA-498 (miR-498) modulates the development of a variety of biological events, including tumorigenesis. Nevertheless, it is unclear whether miR-498 plays a role in CRC. This study was designed to elucidate the underlying mechanism and role of miR-498 in modulation of the viability and invasiveness of CRC cells. We report that CRC tissues and cells exhibited decreased expression of miR-498, and that overexpression of miR-498 resulted in reduced proliferation of CRC cells, concomitant with increased apoptosis. Furthermore, bioinformatic prediction and dual-luciferase reporter assay revealed that miR-498 targeted the 3'-UTR of Bcl-2 for silencing. However, Bcl-2 overexpression suppressed the proapoptosis of miR-498 on CRC cells. In summary, we describe a possible role of miR-498 in CRC, which may lead to the identification of new targets for treatment of this malignancy.