Triple-negative　breast　cancer　(TNBC)　is　regarded　as　the　deadliest　subtype　of　breast　cancer　because　of　its　high　heterogeneity,　aggressiveness,　and　limited　treatment　options.　Toxoflavin　has　been　reported　to　possess　antitumor　activity.　In　this　study,　a　series　of　toxoflavin　analogs　were　synthesized,　among　which　D43　displayed　a　significant　dose-dependent　inhibitory　effect　on　the　proliferation　of　TNBC　cells　(MDA-MB-231　and　HCC1806).　Additionally,　D43　inhibited　DNA　synthesis　in　TNBC　cells,　leading　to　cell　cycle　arrest　at　the　G2/M　phase.　Furthermore,　D43　consistently　promoted　intracellular　ROS　generation,　induced　DNA　damage,　and　resulted　in　apoptosis　in　TNBC　cells.　These　effects　could　be　reversed　by　N-acetylcysteine.　Moreover,　D43　significantly　inhibited　the　growth　of　breast　cancer　patient-derived　organoids　and　xenografts　with　a　favorable　biosafety　profile.　In　conclusion,　D43　is　a　potent　anticancer　agent　that　elicits　significant　antiproliferation,　oxidative　stress,　apoptosis,　and　DNA　damage　effects　in　TNBC　cells,　and　D43　holds　promise　as　a　potential　candidate　for　the　treatment　of　TNBC.