Poly(ADP-ribose) Polymerase 1 (PARP1), one of the most investigated 18 membered PARP family enzymes, is involved in a variety of cellular functions including DNA damage repair, gene transcription and cell apoptosis. PARP1 can form a PARP1(ADP-ribose) polymers, then bind to the DNA damage gap to recruit DNA repair proteins, and repair the break to maintain genomic stability. PARP1 is highly expressed in tumor cells, so the inhibition of PARP1 can block DNA repair, promote tumor cell apoptosis, and exert antitumor activity. To date, four PARP1 inhibitors namely olaparib, rucaparib, niraparib and talazoparib, have been approved by Food and Drug Administration (FDA) for treating ovarian cancer and breast cancer with BRCA1/2 mutation. These drugs have showed super advantages over conventional chemotherapeutic drugs with low hematological toxicity and slowly developed drug resistance. In this article, we summarize and analyze the structure features of PARP1, the biological functions and antitumor mechanisms of PARP1 inhibitors. Importantly, we suggest that establishing a new structure-activity relationship of developed PARP1 inhibitors via substructural searching and the matched molecular pair analysis would accelerate the process in finding more potent and safer PARP1 inhibitors.