Combined with the results from the AOM/DSS-induced in situ CRC mouse model that the expression of ABCG2, TOX3, and WDR5 was elevated in oxaliplatin-resistant tumor tissues, our study provides a robust evidence support to develop TOX3-WDR5/ABCG2 signaling axis as the candidate biomarkers to predict the chemosensitivity and even the clinical outcomes of CRC patients. Here, WDR5 is linked to neoplasm.