Compared with normal cells, cancer cells harbor increased levels of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), and therefore are more vulnerable to further ROS production. This biochemical difference favors the idea of developing new powerful selective prooxidative anticancer agents. However, it still remains a challenge to design them by targeting this difference. Herein, we report the designed dichlorobinaphthoquinone as a prooxidative anticancer agent which is capable of exploiting increased levels of H2O2 of cancer cells to produce in situ lethal hydroxyl radicals (HO•) and thereby kill them selectively, a design strategy inspired from Zhu et al.’s work on the molecular mechanism for metal-independent production of HO•. Display omitted •Designing prooxidative anticancer agents by metal-independent production of HO•.•BQ-DC was designed based on the skeleton of natural conocurvone.•Preferential killing of cancer cells over normal cells by the designed BQ-DC.•BQ-DC can exploit increased levels of H2O2 of cancer cells to in situ produce HO•.•The H2O2-responsive formation of HO• was evidenced by a series of experiments.