Tumor micro‐environment is a critical factor in the development of cancer. The aim of this study was to investigate the inflammatory cytokines secreted by tumor‐associated dendritic cells (TADCs) that contribute to enhanced migration, invasion, and epithelial‐to‐mesenchymal transition (EMT) in colon cancer. The administration of recombinant human chemokine (C‐C motif) ligand 5 (CCL5), which is largely expressed by colon cancer surrounding TADCs, mimicked the stimulation of TADC‐conditioned medium on migration, invasion, and EMT in colon cancer cells. Blocking CCL5 by neutralizing antibodies or siRNA transfection diminished the promotion of cancer progression by TADCs. Tumor‐infiltrating CD11c+ DCs in human colon cancer specimens were shown to produce CCL5. The stimulation of colon cancer progression by TADC‐derived CCL5 was associated with the up‐regulation of non‐coding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT‐1), which subsequently increased the expression of Snail. Blocking MALAT‐1 significantly decreased the TADC‐conditioned medium and CCL5‐mediated migration and invasion by decreasing the enhancement of Snail, suggesting that the MALAT‐1/Snail pathway plays a critical role in TADC‐mediated cancer progression. In conclusion, the inhibition of CCL5 or CCL5‐related signaling may be an attractive therapeutic target in colon cancer patients. J. Cell. Physiol. 230: 1883–1894, 2015. © 2014 Wiley Periodicals, Inc.