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AIMS The purpose of the present study was to analyze the role of selected polymorphisms of SIRT3 and SIRT5 in gastric carcinogenesis. METHODS For this study, 500 blood samples of GC patients and 500 blood samples of healthy individuals were collected. Six selected polymorphisms of mitochondrial sirtuins were analyzed for analysis by Tetra-Arms PCR followed by DNA sequencing. RESULTS Mutant allele frequencies of selected polymorphisms [rs3782116 (p < 0.0001), rs6598072 (p < 0.0001) and rs11246020 (p < 0.0001), rs938222 (p=0.0136), rs3757261 (p=0.0005) and rs2841511 (p=0.0015)] were observed significant higher in GC patients vs controls. Haplotype analysis was performed, and 51 haplotypes were generated using haploview software. Among these haplotypes, eleven haplotypes were found associated with a significantly increased risk of GC. Furthermore, SNP-SNP interaction showed a significant correlation between studied SNPs and GC risk. Kaplan Meier analysis showed that mutant allele frequencies of selected polymorphisms are linked with a significant decrease in survival of GC patients. CONCLUSIONS It can be concluded that selected SNPs may be associated with enhanced risk of GC and hence can be potential prognostic markers for prognosis and predisposition of GC.