This systematic review and cumulative analysis aimed to explore the efficacy and safety of the combination of intravesical mitomycin C (MMC) plus bacillus Calmette-Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC) patients. A comprehensive literature search using Pubmed, Embase, Medline, Cochrane Library, CBM, CNKI and VIP databases was performed to identify studies applying intravesical MMC plus BCG therapy on NMIBC patients up to June 2016. Summarized unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the efficacy and safety of the combination therapy. A total of 25 studies containing 2749 NMIBC patients were included in this systematic review. Compared with BCG monotherapy, the combination therapy could significantly reduce the tumor recurrence rate (OR = 0.64, 95% CI: 0.44-0.94, P = 0.02) and cancer-specific mortality (OR = 0.54, 95% CI: 0.34-0.87, P = 0.01), without more toxicities (OR = 0.58, 95% CI: 0.17-1.94, P = 0.37). The combination therapy could also lead to significant lower tumor recurrence rate than MMC monotherapy (OR = 0.41, 95% CI: 0.24-0.69, P = 0.0009). Our study indicates that the combination of MMC plus BCG instillation is an effective and safe adjuvant treatment for NMIBC patients.