Chloroethylnitrosoureas　(CENUs)　are　clinically　useful　anticancer　agents.　Their　cytotoxicity　is　associated　with　the　generation　of　DNA　interstrand　crosslinks.　QM/MM　computations　are　carried　out　to　investigate　DNA　crosslinks　by　CENUs　with　ONIOM　hybrid　method.　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　deformation　of　DNA　with　dG(N-1)-dC(N-3)　crosslink　is　much　less　than　the　other　crosslinks,　which　indicate　that　the　most　favorable　crosslink　is　between　the　N-1　atom　of　guanine　and　the　N-3　atom　of　the　complementary　cytosine.