Even though our and others’ previous studies show that FEN1 deficiency/inhibition and PARP1 inhibition synergistically kill cancer cells (Hanzlikova et al., 2018; He et al., 2016), our new observations suggest that the efficacy of combined FEN1 inhibition and PARP1 inhibition in killing cancer cells may at least partly depend on LIG1 status. The gene discussed is FEN1; the disease is cancer.