Decoy receptor 3 (DcR3) is considered to have anti‑apoptotic and pro-metastatic functions, suggesting it might be a therapeutic target. We examined the role and mechanisms of DcR3 on growth and the metastatic ability of SW480 colon cancer cells to provide therapeutic information for targeting DcR3 by RNA interference (RNAi) technology. Growth and the metastatic ability were inhibited, apoptosis was induced and cell cycle profile was changed after decreasing DcR3 expression, with lower levels of vascular endothelial growth factors (VEGFs) and matrix metalloproteinases (MMPs) expression. Our results implied the therapeutic potential of silencing DcR3 expression by RNAi in colon cancer.