Despite the potential importance of apoptosis pathways in prostate tumor etiology, little has been published regarding prostate tumor risk associated with common gene variants in caspases (CASP). Normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk.Using data from a hospital-based case-control study conducted by Sanjay Gandhi Post Graduate Institute of Medical Science, India, from 2007 to 2009, we evaluated risk of prostate cancer (CaP) in 165 patients and age-matched 205 healthy controls. We genotyped the functional IVS12-19G/A, D302H, -678del, and -652 6N ins/del polymorphisms in the promoter of CASP 8 and -293del, -1263A/G in CASP 9 genes.A significant increased risk for CaP was found for the CASP 8 IVS12-19G/A heterozygous genotype (P = 0.02; OR = 1.69) as well as for the variant allele carriers (P = 0.04; OR = 1.56). Also the CASP 9 -1263A/G showed lower risk for both heterozygous and variant allele carrier genotypes (P = 0.002; OR = 0.45 and P = 0.05; OR = 0.66 respectively). CASP 9 -1263A/G was also found to be associated with increased risk with bone metastasis. Furthermore, a significant additive interaction between CASP 8 IVS12-19G/A polymorphism and tobacco smoking was observed with CaP risk.These results suggested that the CASP 8 IVS12-19G/A and CASP 9 -1263 polymorphism may be involved in etiology of CaP and thus could be implicated as a marker for genetic susceptibility in North Indian population.