Abstract: Objective To investigate the expressions of secreted frizzled-related protein 4 (SFRP4) in stage II DNA mismatch repair-deficient (dMMR) and mismatch repair- proficient (pMMR) colorectal cancers and explore their clinical significance. Methods We collected fresh stage II colon cancer tissues with different MMR status detected by immunohistochemistry (IHC). The differentially expressed mRNAs between dMMR and pMMR tumors were identified by Affymetrix Human oeLncRNA gene chip, and the expression of SFRP4 in these cancer tissues and in colorectal cancer cell lines were detected using Western blotting and real- time quantitative PCR. The apoptosis rates of HCT116 cells with and without siRNA- mediated transient SFRP4 knockdown were determined using flow cytometry. We further investigated the expression pattern of Ki-67 and its correlation with SFRP4 expression. Results Compared with pMMR colon cancer tissues or cells, both dMMR colon cancer tissues (P=0.014) and cells (P=0.0079) showed significantly increased expression of SFRP4, which was in negative correlation with Ki-67 (P=0.041). In HCT116 cells, transient SFRP4 knockdown resulted in decreased cell apoptosis, including both early apoptosis (P=0.003) and late apoptosis (P=0.024). Conclusion Up-regulation of SFRP4 in dMMR stage II colon cancer promotes apoptosis and inhibits proliferation of the cancer cells, and may improve the prognosis of dMMR colon cancer.