Background: Attenuated live bacterial therapy and medical BSA materials have their own advantages in anti-cancer research, and their combination is expected to overcome some of the disadvantages of conventional anti-cancer therapeutics. Methods and objective: Utilizing the high affinity between biotin and streptavidin, BSA modification on the surface of Escherichia coli (E. coli) was achieved. Then, the adhesion and targeting abilities of BSA modified E. coli was explored on different bladder cancer cells, and the underlying mechanism was also investigated. Results: BSA modification on the surface of E. coli enhances its ability to adhere and target cancer cells, and we speculate that these characteristics are related to the expression of SPARC in different bladder cancer cell lines. Conclusion: BSA and live bacteria have their own advantages in anti-cancer research. In this study, we found that E. coli surface-modified by BSA had stronger adhesion and targeting effects on bladder cancer cells with high expression of SPARC. These findings pave the way for the future studies exploring the combination of BSA combined with live bacteria for cancer therapy.