In summary, this study proposed an oxidative stress-related signature composed of ACOX1, CPT2, NAT2, NRG1, PPARGC1A, CDKN2A, CRYAB, NGFR, and UCN to predict clinical outcomes and therapeutic responses of CRC patients, which provided valuable information for understanding the functional roles of oxidative stress in CRC development, assisting prognosis prediction and guiding adjuvant therapy (especially small molecular compounds and immunotherapy), thereby facilitating precision oncology of CRC. Here, CDKN2A is linked to colorectal carcinoma.