In this study, we employed a CRISPR/Cas9 sgRNA library targeting 1,117 human ubiquitination-related genes to screen key regulators of sensitivity to Oxa and identified the Makorin Ring Finger Protein 1 (MKRN1), an E3 ligase, as an Oxa-resistant gene of CRC cells. This evidence concerns the gene MKRN1 and colorectal carcinoma.