We found the following: (i) PRDX2 is highly expressed in CRC and other cancers, (ii) depletion of PRDX2 mediates p38/FOXO-pathway regulation of the cell cycle and autophagy, (iii) loss of PRDX2 causes cell arrest in S phase and impairment of autophagy flux, (iv) PRDX2 is associated with cell-cycle and autophagy phenotypes in CRC patients, and (v) PRDX2 functions through the p38/FOXO pathway to impact the cell cycle and autophagy in an in vivo CRC mouse model. The gene discussed is MAPK1; the disease is colorectal carcinoma.