Objective The aim of the study was to investigate whether colon cancer stem cells induced by epidermalgrowth factor (EGF) to enter the cell cycle enhanced the chemosensitivity of colon cancer.Methods In vitro, EGF was used to stimulate the entry of human colon cancer HCT116 cells into the cellcycle. Before and after treatment with EGF, CD133+ HCT116 cells were collected and flow cytometry wasconducted to determine the apoptosis rate based on the 5-Fu and Ki-67 expression rates. The cell cycledistribution of the two groups was also determined. In vivo, a subcutaneous xenograft model of HCT116human colon cancer cell lines in nude mice was established. The nude mice were divided into two groupsand treated with EGF and 5-Fu, respectively. Differences in the growth of implanted tumors revealed theefficiency of cycle-induction combined chemotherapy.Results (1) After EGF stimulation, the S-G2/M proportion of CD133+ HCT116 cells and Ki67 expressionwere increased, indicating that more cancer stem cells entered the cell cycle and promoted proliferation; (2)After EGF stimulation, CD133+ HCT116 cells showed a higher apoptosis rate induced by 5-Fu. (3) Animalexperiments showed that the group subjected to combined treatment with EGF and 5-Fu had smaller tumorsizes compared to the group treated with 5-Fu alone.Conclusion EGF enhanced tumor sensitivity to chemotherapeutic drugs, likely by promoting tumor stemcells to enter the cell cycle.