Then, we established TRIM9 overexpressed bladder cancer mice model, verified the pro-tumor function in vivo, and suggested that the blockage of Smad2/3 signaling significantly improved the chemotherapy outcome in bladder cancer, which highlighting the potential clinical significance of TRIM9/Smad2/3 signaling in bladder cancer. The gene discussed is SMAD2; the disease is urinary bladder carcinoma.