1,2-Dichloropropane　(1,2-DCP)　is　used　as　an　industrial　solvent,　insecticide　fumigant　and　household　dry　cleaning　product.　Carcinogenicity　caused　by　long-term　exposure　to　1,2-DCP　is　well　established.　However,　the　possible　liver　damage　and　related　toxic　mechanisms　associated　with　acute　inhalation　exposure　to　1,2-DCP　are　rarely　reported.　In　this　study,　we　investigated　the　effects　of　individual　and　combined　exposure　to　1,2-DCP　and　dichloromethane　(DCM)　on　mice　liver.　The　results　showed　that　1,2-DCP　significantly　caused　liver　necrosis,　possibly　due　to　1,2-DCP-induced　inhibition　of　the　mitochondrial　respiratory　chain　complex　I-IV　activities,　resulting　in　mitochondrial　dysfunction　and　extreme　ATP　consumption.　Moreover,　1,2-DCP　also　decreased　mitochondrial　defense　ability　by　inhibiting　the　mitochondrial　glutathione　S-transferase　1　(MGST1)　activity,　further　aggravating　liver　damage.　Additionally,　we　found　that　DCM　co-exposure　potentially　enhanced　1,2-DCP　toxicity.　Our　findings　suggest　that　inhibition　of　mitochondrial　function　and　MGST1　activity　play　critical　roles　in　modulating　1,2-DCP-induced　liver　damage.　Furthermore,　our　results　contribute　to　study　the　new　mechanism　of　mitochondria-dominated　signaling　pathways　underlying　liver　injury　induced　by　1,2-DCP　and　DCM.　©　2018　John　Wiley　&　Sons,　Ltd.