Herein, we utilized bioinformatics analysis, tissue chips, molecular biology methods, matrix stiffness assays, and animal experiments to explore the function of the mechanical axis Piezo1/ITGB1/YAP in BLCA development and ECM remodeling, aiming to search for a promising way and novel tactic for BLCA management. Here, PIEZO1 is linked to bladder transitional cell carcinoma.