The cause of skin toxicity was HFSR induced by previous administration of VEGFR inhibitor in 15 patients (42.9%); and hand-foot syndrome induced by previous fluoropyrimidine, anti-epidermal growth factor receptor (EGFR) antibody, and trifluridine-tipiracil in 16 patients (45.7%); and others in 4 patients. The gene discussed is KDR; the disease is Hand-foot syndrome.