Perturbations in the cell cycle and apoptotic genes have been implicated in human malignancies. Cell cycle (MDM2 and Cyclin D1) and apoptotic (Fas) genes that are differentially expressed in urinary bladder cancer (UBC) were investigated with the susceptibility to UBC in northern India. A total of 212 UBC patients and age- and sex-matched 250 controls were investigated for MDM2 G309T, Cyclin D1 G870A, and Fas A670G polymorphisms by polymerase chain reaction and restriction fragment length polymorphism. MDM2 309GG was at reduced risk for developing UBC when compared with TT genotype (p = 0.027; odds ratio, 0.55). GG genotype was also associated with reduced risk in nonmuscle invasive bladder cancer (NMIBC) and muscle invasive BC (p = 0.006 and p = 0.049). Cyclin D1 AA genotype was associated with high risk in NMIBC (intermediate risk) stage (p = 0.015; odds ratio, 4.55). MDM2-Cyclin D1 interaction revealed overall protective effect. The GG genotype of MDM2 also showed a protective effect and high recurrence-free survival in Bacillus Calmette-Guerin-treated NMIBC patients (log rank p = 0.008). MDM2 GG genotype had protective effect and MDM2T309G polymorphism had profound influence in Bacillus Calmette-Guerin-treated UBC patients in the North Indian population.