Simmiparib potently inhibits PARP 1/2 and traps PARP 1-DNA complexes. Simmiparib induces DSB accumulation and G2/M arrest in HR-deficient cells. Simmiparib selectively induces apoptosis in HR-deficient cells. Simmiparib exhibits remarkable anticancer activities both in vitro and in vivo. Simmiparib sensitizes HR-proficient cancer cells to anticancer drugs.