Chloroethytnitrosoureas　(CENUs)　are　clinically　useful　anticancer　agents.　Their　cytotoxicity　has　been　proved　to　be　associated　with　the　generation　of　DNA　interstrand　crosslinks.　In　the　present　work,　QM/MM　computations　are　carried　out　to　investigate　the　crosslinks　of　DNA　complementary　bases　by　the　CENUs　with　ONIOM　hybrid　method.　DNA　double　helix　containing　crosslinked　base　pairs　are　established　as　the　computational　models.　The　crosslinked　DNA　are　subdivided　into　three　layers,　each　of　which　are　described　at　B3LYP/6-311+G(d,p),　AM1　and　UFF　level　of　theory　respectively.　The　result　shows　that　the　covalent　crosslink　between　guanine　M　and　complementary　cytosine　N-3　is　the　most　favorable　crosslinking　product.　This　crosslink　is　characterized　by　its　less　deformation　of　DNA　double　helix　and　higher　stability　than　the　other　crosslinks　on　the　complementary　base　pairs.　The　results　of　the　ONIOM　computations　explain　the　phenomenon　that　1-(N-3-deoxycytidyl)-2-(N-1-deoxyguanosinyl)ethane　is　the　main　crosslink　product　in　the　in　vivo　an　the　in　vitro　experiments.