A novel target-promoted DNA alkylation system was designed, which consists of a DNA intercalating/alkylating quinone methide (QM) precursor, a removable amine linker, and a sequence-specific delivery. The QM in this system was regenerated by eliminating the amino linker promoted by the hydrophobic interaction between the target DNA and the intercalating QM precursor. Three alkylation model systems (methoxyl polycyclic system, intramolecular hydrogen bonding system and biaryl system) were proposed and synthesized. The potential DNA QM alkylation was investigated by deoxyadenosine (dA) and deoxyguanosine (dG) alkylation with the biaryl system. Only one deoxynucleoside adduct was observed when dA or dG reacted with quinoline or naphthalene QM precursor, in which both dA adducts degraded with time, while dG adducts remained unchanged after 72h at room temperature. The quinoline dG adduct was fully characterized as quinoline dG N1 adduct by NMR techniques. Naphthalene dG was found as a 1:1 mixture of diastereomers.