Our results revealed that Exo-hypoxic and Exo-normoxic significantly promote the proliferation of CRCs with greater proliferation induced by Exo-hypoxic than by Exo-normoxic, which is probably because Exo-hypoxic induce stronger STAT3 activation and shorter mitosis duration in colon cancer cells than normoxic as demonstrated in the current studies. Here, STAT3 is linked to malignant colon neoplasm.