Accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with disease outcome. Our team investigated the prediction power of D-loop SNPs in non-small cell lung cancer (NSCLC) outcome. In an overall multivariate analysis, allele 16390 was identified as an independent predictor for NSCLC outcome. The length of survival of patients with allele 16390A was significantly shorter than that of patients with allele 16390G (relative risk, 0.323; 95% CI, 0.109-0.951; p=0.040). The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify NSCLC patient subgroups at a high risk for a poor disease outcome.