Abstract: Objective:To examine the expression of CLC-3 in colorectal tissues and the effect of CLC- 3 on the viability and invasion of colorectal cancer (CRC) SW 480 and SW620 cells.Methods:The mRNA levels of CLC- 3 in CRC cell lines were determined by RT-PCR. CLC-3 expression was inhibited by adding DIDS or NPPB to the CRC cells. Subsequently, cell viability and invasion were assessed by CCK- 8 assay and Transwell assay, respectively. In addition, the effects of DIDS and NPPB on the Wnt or β -catenin signaling pathways were de -termined by Western blot analysis. Results:The mRNA level of CLC- 3 was remarkably increased in the CRC tissues compared with that in normal colorectal tissues ( P<0. 05) and was positively correlated with the T stage of CRC. The blockade of CLC- 3 inhibited the viability and invasion of CRC cells ( P<0. 05). The expression of β -catenin, C-myc, cyclin D 1, Ki- 67, and survivin were evidently reduced by the in-hibition of CLC-3 (P<0. 05). Conclusion: The inhibition of CLC- 3 decreases the cell viability and invasion of CRC cells by reducing the ex -pression of the proteins related to the Wnt or β -catenin signaling pathway.