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Objectives Mitochondrial dysfunction has long been associated with the pathogenesis of lung cancer (LC). Mitochondrial DNA (mtDNA) haplogroups have been reported to modify the risk of LC in a few different populations; however, no study has been done among the Indians. Here, we explore the relationship between mtDNA haplogroups and LC in a representative eastern Indian sample set. Methods Different combinations of six mtDNA SNPs, which define the major Asian mtDNA haplogroups M and N, and their sub-haplogroups D, G, M7, R, and F were genotyped via polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) – sequencing approach in 94 smoker LC patients and 100 healthy smoker controls from an eastern Indian cohort. Results The distribution of 7 mtDNA haplogroups did not show any significant differences between patients and controls (p Conclusions Our study is the first to indicate that the major Asian mtDNA haplogroups have no significant (p<0.05) association with LC in East Indian population.