The effect of endogenous expression of the laminin α5 chain on the phenotype of colorectal cancer cells has been studied. For this purpose, the knockdown of LAMA5 gene coding for the α5 laminin chain in the HT29 colorectal adenocarcinoma cell line was carried out. The data on gene expression at both mRNA and protein levels indicate that the α5 laminin chain is involved in the regulation of cell differentiation. For example, a decrease in the expression of such markers of differentiation of the intestinal epithelium as SI, KRT20, ANXA13 and MUC13 was observed. In addition, the expression of the intestinal epithelial stem cell marker LRG5 and CD44 transmembrane protein was increased. Changing the phenotype of HT29 cells may be a result of the effect of the laminin α5 chain on the activity of the Wnt signaling pathway.