Human T-cell Lymphotropic virus type-1 (HTLV-1) is endemic in Northeast of Iran. Still, it is unclear that genetic background has role in infection by HTLV-1. Methods: We ascertained the frequency of mitochondrial DNA (mtDNA) D-loop region nucleotide changes in 45 HTLV-1 infected individuals and 463 healthy control subjects using Sanger sequencing method. Results: Out of totally 164 identified single nucleotide polymorphisms (SNPs) among HTLV-1 patients, 89 SNPs found statistically significant in comparison to the control group (P<0.05). In this study, no deletion was identified in mtDNA D-loop region. But, for the first time a high frequency of point mutations was observed in HTLV-1 patients. Conclusion: Such nucleotide changes in HTLV-1 patients propose that these mutations may result in impaired mitochondria function directly and/or indirectly. Moreover, these variations may act as a predisposing factor along with the environmental factors, and might play an important role in pathogenesis of HTLV-1.