This study aims to investigate the precise impact of MTDH on CRC radio-resistance.<h4>Methods</h4>Through a fusion of 14 machine learning algorithms and SHapley Additive exPlanations (SHAP) interpretability analysis, we pinpointed MTDH as a pivotal gene implicated in radio-resistance mechanisms. The gene discussed is MTDH; the disease is colorectal carcinoma.