Single-walled　carbon　nanotubes　(SWCNTs)　are　broadly　used　for　various　biomedical　applications　such　as　drug　delivery,　in　vivo　imaging,　and　cancer　photothermal　therapy　due　to　their　unique　physiochemical　properties.　However,　once　they　enter　the　cells,　the　effects　of　SWCNTs　on　the　intracellular　organelles　and　macromolecules　are　not　comprehensively　understood.　Cytochrome　c　(Cyt　c),　as　a　key　component　of　the　electron　transport　chain　in　mitochondria,　plays　an　essential　role　in　cellular　energy　consumption,　growth,　and　differentiation.　In　this　study,　we　found　the　mitochondrial　membrane　potential　and　mitochondrial　oxygen　uptake　were　greatly　decreased　in　human　epithelial　KB　cells　treated　with　SWCNTs,　which　accompanies　the　reduction　of　Cyt　c.　SWCNTs　deoxidized　Cyt　c　in　a　pH-dependent　manner,　as　evidenced　by　the　appearance　of　a　550　nm　characteristic　absorption　peak,　the　intensity　of　which　increased　as　the　pH　increased.　Circular　dichroism　measurement　confirmed　the　pH-dependent　conformational　change,　which　facilitated　closer　association　of　SWCNTs　with　the　heme　pocket　of　Cyt　c　and　thus　expedited　the　reduction　of　Cyt　c.　The　electron　transfer　of　Cyt　c　is　also　disturbed　by　SWCNTs,　as　measured　with　electron　spin　resonance　spectroscopy.　In　conclusion,　the　redox　activity　of　Cyt　(was　affected　by　SWCNTs　treatment　due　to　attenuated　electron　transfer　and　conformational　change　of　Cyt　c,　which　consequently　changed　mitochondrial　respiration　of　SWCNTs-treated　cells.　This　work　is　significant　to　SWCNTs　research　because　it　provides　a　novel　understanding　of　SWCNTs＇　disruption　of　mitochondria　function　and　has　important　implications　for　biomedical　applications　of　SWCNTs.