Methyltransferase-like 3 (METTL3) belongs to the class I MTase family, and it has been proved that METTL3 is highly expressed in a variety of tumors and promotes tumor progression. Our previous studies have shown that METTL3 is highly expressed in gastric cancer tissues compared with para-cancer tissues, and its expression level is negatively correlated with good postoperative prognosis of patients. To explore the expression of METTL3 in colorectal cancer (CRC) tissue and the relationship between METTL3 and the clinicopathologic features and prognosis of CRC patients. The expression of METTL3 in cancer tissues and adjacent tissues of 180 patients with colorectal cancer was analyzed by tissue microarray and immunohistochemistry. The clinicopathologic features of patients with different METTL3 expression levels were analyzed. The expression level of METTL3 in colorectal cancer tissues was higher than that in adjacent tissues (P < .05). There were statistically significant differences in the expression of METTL3 in clinical stage, survival time and distant metastasis (all P < .05). The expression level of METTL3 in colorectal cancer tissues with tumor-node-metastasis stage III and IV and distant metastasis was higher than that in clinical stage I and II and without distant metastasis (P < .05). Patients with high METTL3 expression had a higher overall mortality rate compared to patients with low METTL3 expression, and the difference was statistically significant (P < .05). Univariate Cox regression analysis suggested that tumor distant metastasis, vascular invasion, pathological grade, lymph node metastasis and METTL3 expression level were risk factors for overall survival in CRC patients (all P < .05). Multivariate Cox regression analysis suggested that low pathological grade (hazard ratio = 1.695, 95% confidence interval: 1.116-2.274, P = .005) and high METTL3 expression (hazard ratio = 2.156, 95% confidence interval: 1.587-2.725, P < .001) could be used as independent risk factors for prognosis assessment. The expression of METTL3 was increased in colorectal cancer, and METTL3 was closely related to clinical stage, distant metastasis and prognosis of colorectal cancer.