Our study revealed that xCT knockdown effectively suppressed the sphere-forming capability of CRC cells, and the expression of stemness-related factors such as CD133 and EPCAM was significantly downregulated with xCT knockdown in both CRC cells and tumor tissues, indicating that xCT knockdown plays a crucial role in suppressing the stemness of CRC cells. This evidence concerns the gene EPCAM and colorectal carcinoma.