Colorectal cancer (CRC) is one of the most predominant solid carcinomas in Western countries. However, there is conflicting information on the effects of soy isoflavone on CRC risk. Therefore, we performed a meta-analysis to assess the association between soy isoflavone consumption and CRC risk in humans using PubMed, Embase, Web of Science, and Cochrane Library databases. A total of 17 epidemiologic studies, which consisted of thirteen case-control and four prospective cohort studies, met the inclusion criteria. Our research findings revealed that soy isoflavone consumption reduced CRC risk (relative risk, RR: 0.78, 95% CI: 0.72-0.85 I2 = 34.1%, P = 0.024). Based on subgroup analyses, a significant protective effect was observed with soy foods/products (RR: 0.79; 95% CI: 0.69-0.89), in Asian populations (RR: 0.79; 95% CI: 0.72-0.87), and in case-control studies (RR: 0.76; 95% CI: 0.68-0.84). Therefore, soy isoflavone consumption was significantly associated with a reduced risk of CRC risk, particularly with soy foods/products, in Asian populations, and in case-control studies. However, due to the limited number of studies, other factors may affect this association.