In this study, we demonstrated that IL-18 alone did not affect HCT116 cells but promoted the antitumor ability of NK cells in a coculture with HCT116 cells via the miR-574-3p/TGF-β1 axis; this finding suggests that IL-18 can be the new potential target for cancer immunotherapy for CRC. This evidence concerns the gene IL18 and colorectal carcinoma.