Abstract: In recent years, accumulating studies in cancer stem cells niche gradually opened an era of “niche time”. As one of the classical solid tumors, colorectal cancer presented a relatively clear process of cancer initiating and development, which would be an ideal model for niche research. Paneth cells, which play a key role in supporting and protecting the intestine stem cells, are important element of normal intestinal epithelium and also one of the major components of the stem cells niche. However, the potential role of these cells, take the Paneth cells for example, on the road of colorectal epithelium malignant transformation are still largely unknown. Further studies aimed to uncover the relationship of Paneth cells with the intestine stem cells and its role in different stages of colorectal tumor development could expand the knowledge of cancer stem cells niche, also, could help to find the potential new therapeutic targets for colorectal cancer treatment in future.