Objective To explore the relationship between meteorin-like protein (Metrnl) and colorectal cancer and its role in the development and progression of colorectal cancer. Methods Expression and distribution of Metrnl in the colorectal cancer and paracancerous tissue were analyzed by human tissue microarray (n＝30). Fifteen clinical colorectal cancer tissue samples and 15 normal human colorectal tissue samples were collected, and the expression level of Metrnl mRNA was detected by quantitative polymerase chain reaction. In the cell experiment, the expression of Metrnl in human colon cancer epithelial cell line Caco-2 was knocked down by lentivirus-mediated short hairpin RNA (shRNA) interference technology (Metrnl shRNA group), and unrelated sequence was used as control (Scr shRNA group). Cell counting kit 8, cysteine aspartic acid specific protease 3 (caspase 3) activity assay kit and annexin Ⅴ-fluorescein isothiocyanate/propidium iodide flow cytometry apoptosis detection kit were used to detect the cell viability and apoptosis under the treatment of 5-fluorouracil. Results Metrnl protein was significantly higher in the human colorectal cancer tissue compared with the paracancerous tissue (P＜0.000 1), but the level of Metrnl mRNA in the colorectal cancer tissue was significantly lower compared with the normal colorectal tissue (0.09±0.02 vs 0.22±0.06, P＜0.05). Knockdown of Metrnl blocked the decline of cell viability induced by 5-fluorouracil (P＜0.05). The activity of caspase 3 and the proportion of apoptotic cells in the Metrnl shRNA group were significantly lower than those in the Scr shRNA group (1.04±0.27 vs 1.67±0.44, ［12.53±6.69］% vs ［26.56±10.89］%, both P＜0.05). Conclusion Secretory protein Metrnl is accumulated in the colorectal cancer tissue, but Metrnl transcription decrease in colorectal cancer may promote the development and progression of colorectal cancer.