By using the well-recognized cell surface markers of CD44 and CD133 for CSC identification, we tried to separate the HCT8 human colon cancer cells into CD44−, CD44+, CD44+CD133−, and CD44+CD133+ subpopulations and then investigated how the expressions of CD44 and CD133 associated with drug resistance. This evidence concerns the gene PROM1 and malignant colon neoplasm.