To ensure the effects of CD44 on the Wnt/β-catenin signaling pathway in CRC cells, we down-regulated the CD44 expression by siRNA, and found that the phosphorylation level of GSK3β and total β-catenin level decrease, the phosphorylation level of β-catenin increases, and the invasion ability of TRIM29 transfected RKO cells is weakened. The gene discussed is TRIM29; the disease is colorectal carcinoma.