In summary, we demonstrate in the current study that α5 integrin subunit was mainly located in the colorectal tumor fibroblasts, and we provide evidence that α5 expression is required for fibroblasts to exhibit a tumor‐promoting effect, as α5 depletion in fibroblasts dramatically suppresses fibroblast‐induced tumor growth in xenograft nude mice and inhibits cancer cell migration and invasion induced by fibroblasts in in vitro coculture assays. This evidence concerns the gene IGKV2D-26 and colorectal neoplasm.