Our aim was to compare the effects of Tcf-4 knockdown and β-catenin knockdown on cell proliferation, apoptosis, and chemosensitivity in the SW480 (mutant APC, wild-type CTNNB1) and HCT116 (mutant CTNNB1, wild-type APC) colon cancer cell lines using short hairpin RNA (shRNA). This evidence concerns the gene APC and malignant colon neoplasm.