Food nutrition and human health are still interesting international issues. Early detection, risk assessment and diet are vital to mitigate the load of intestinal diseases and enhance the quality of life. Plant-derived microRNAs could be transferred to mammalian organisms by cross-kingdom regulation which adjusts relevant target genes for their participation in the process of carcinogenesis. But the mechanism of plant-derived microRNAs in colorectal cancer is still unclear. This review aims to summarize the current pathways of plant-derived microRNAs in colorectal cancer including intestinal bacteria, the tumor microenvironment, plant active substances and protein, discuss the direct or indirect effects of plant-derived microRNAs on the occurrence and/or progression of colorectal cancer and explain why plant-derived microRNAs can be used as a potential anti-cancer agent. Moreover, the drawbacks of plant-derived microRNAs are also discussed in terms of both edible plants and synthetic delivery vectors for RNAi interference technology for human disease treatment. This review will provide a potential way for plant-derived microRNAs to target colorectal cancer.