The RNA 5-methylcytosine (m5C) methyltransferase NSUN2 has been implicated in tumor progression, but its role in CRC chemoresistance remains unclear.<h4>Methods</h4>We investigated the functional and mechanistic involvement of NSUN2 in CRC progression and OXA response, focusing on ferroptosis-related pathways. Here, NSUN2 is linked to neoplasm.