Cancer is a major threat to the lives and health of people around the world, and the development of effective antitumor drugs that exhibit fewer toxic effects is an important aspect of cancer treatment. PARP inhibitors are antitumor drugs that target pathways involved in DNA-damage repair. The currently approved PARP inhibitors include olaparib, niraparib, rucaparib, talazoparib, fuzuloparib, and pamiparib. Hematological toxicities associated with the simultaneous inhibition of PARP-1 and PARP-2 have limited the clinical applications of these drugs. The present review introduces the necessity for research on the development of selective PARP-1 inhibitors from the perspective of structural and functional mechanisms of PARP-1 inhibition. A review of recently reported selective PARP-1 inhibitors provides the foundation for exploring novel strategies for designing selective PARP-1 inhibitors from the perspective of structure-activity relationships combined with computer simulations.