Problem statement: Bladder cancer is a common urologic cancer and intravesical Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the mainstay in the treatment of superficial bladder cancer. However, the current BCG therapy is not desirable with respect to its efficacy and side effects. Interleukin (IL)-10, a T helper type (Th) 2 cytokine, plays an important regulatory role in bladder cancer immunosurveillance and BCG immunotherapy. Therefore, blocking IL-10 activity could be beneficial for bladder cancer patients undergoing BCG therapy. Approach: Treatment with intravesical BCG in combination with systemic IL-10 monoclonal antibody (mAb) specific for IL-10 neutralization or IL-10 receptor (IL-10R) blockage has been evaluated in preclinical bladder cancer models. Results: Addition of anti-IL-10 neutralizing mAb or anti-IL-10R1 mAb enhances BCG induction of Th1 immune responses and anti-bladder cancer immunity. Conclusion/Recommendations: BCG immunotherapy of bladder cancer can be enhanced by addition of IL-10 blocking mAb. Future studies should aim to explore the mechanisms underlying the induction of enhanced antitumor immunity by BCG combination therapy and develop therapeutic regimens for clinical evaluation of the safety and efficacy of BCG combination therapy.