Background Cancer stem cells (CSCs) are a type of tumor cell that are self-sustaining and can differentiate into several different types of cells. The present study aims to investigate the effect of hematopoietic progenitor cells (HPCs) on the biological behavior of colon CSCs (CCSCs) and to determine the underlying molecular mechanisms of liver metastasis in colorectal cancer. Methods Subsets of CCSCs were isolated from stem-like HCT116 cells and cocultured with CD133 + HPCs in vitro. Colony formation assay, and CCK-8 were used to assess the effects of HPCs on CCSC subsets. Invasive and migration assay were done to study the effects of HPCs mediated metastatic capacity of CCSC subsets. Expression of MMP-9, VEGF, E-cadherin and β-catenin was analyzed by qPCR and Western blotting. Results CCK-8 and colony formation assays showed that HPCs significantly promoted proliferation and colony formation of the CCSC subsets (P=0.031). HPCs also significantly enhanced the migration (P=0.011) and invasive capacity (P=0.001) of the CCSC subsets. Quantitative PCR showed that MMP-9 and VEGF expression in CCSC subsets were significantly upregulated (P=0.000 and P=0.005). Western blotting showed that MMP-9, VEGF and β-catenin expression in CCSC subsets were significantly upregulated (P=0.000, P=0.005, P=0.000). The protein expression levels of E-cadherin in the CCSC subsets was significantly downregulated (P=0.002). Conclusions CD133 + HPCs enhanced migration, invasion and proliferation of CCSC subsets in vitro .