Reactive species (RS) are the molecules responsible for cancer cell cytotoxicity in chemotherapy and radiotherapy. The efficient elimination of cancer cells in cancer therapy relies on the effective production of oxygen-derived reactive species, especially superoxide and hydroxyl. In addition, oxygen modulates the inherent time-keeping mechanism by clock genes and redox oscillators. Earlier studies in our lab discovered rhythms in RS levels in cancer cells. Although the tumor microenvironment is hypoxic (2% oxygen), most studies investigating the link between oxygen and redox-based time-keeping mechanisms have been conducted under normoxia (21% oxygen in the air). In this study, we show that hypoxia entrains (resets/alters/remodels/realigns) the redox rhythms in a cell line model of colorectal cancer, HCT116, compared to normoxia. Contrary to the circadian or near circadian redox rhythms observed under normoxia in HCT116 cells, we found that hypoxia remodels the redox rhythms, i.e. rhythms of superoxide, hydroxyl, and superoxide dismutase, in different ways. Further, we studied the effect of hypoxia on the growth of colon cancer cell line HCT116 and the efficiency of the redox-active anticancer drug, menadione. The results suggest that hypoxia-mediated entrainment of redox rhythms could enhance therapeutic resistance during colon cancer chronotherapy. In addition, we are in the process of analysing the metabolic aspects through a genome-scale metabolic model to better understand and further improve the effectiveness of appropriate cancer therapies.