Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Along with chemotherapy, anti-EGFR monoclonal antibodies are the first-line treatment for RAS- and BRAF-wild- type metastatic CRC, but many patients have primary or secondary resistance to these drugs, which limits their efficacy. In some patients, this resistance may involve noncoding RNAs. making these nucleic acids promising biomarkers or targets for anti-EGFR antibody sensitization. For example, the miRNAs miR-100 and miR-125b are upregulated in CRC resistant to the anti-EGFR drug cetuximab. These miRNAs and the upregulated lncRNA MIR100HG synergistically activate the Wnt/β-catenin pathway to promote resistance. In contrast, the tumor-suppressor miRNA miR-7 is downregulated in cetuximab-resistant CRC and the overexpressed circRNA circHIPK3 may contribute to this downregulation by sponging miR-7. These types of interactions create complex regulatory networks beyond the individual effects of the noncoding RNAs, but the details are far from clear. Further mechanistic research will help clarify the various roles of noncoding RNAs in anti-EGFR resistance and may ultimately help improve survival in patients with CRC.