Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer risk. We investigated the malignant melanoma (MM) risk profile of D-loop SNPs in a case-controlled study in Chinese Han population. A statistically significant increase in SNP frequency for the T16362C, A16399G and T195C alleles was observed in MM patients (p < 0.05) comparing the MM patients to controls, which indicted that the patients who carry these alleles were susceptible to MM. The study identified SNPs in the mitochondrial D-loop could increase MM risk in Chinese Han people. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a higher risk of developing MM in Chinese Han population, thereby helping to make therapeutic decisions for these patients.