We introduced the specific mutations of MLL into bladder cancer cells with the method of CRISPR/Cas9 and the mutated cell exhibited enhanced H3K4me3 modification and elevated expression of GATA4 and ETS1 downstream, which endowed bladder cancer cells with the capability of drug-resistance to chemotherapy drug epirubicin. The gene discussed is GATA4; the disease is urinary bladder cancer.