Although DNA damage repair plays a critical role in cancer chemotherapy, the function of lncRNAs in this process remains largely unclear. In this study, in silico screening identifiedH19as an lncRNA that potentially plays a role in DNA damage response and sensitivity to PARP inhibitors. Increased expression ofH19is correlated with disease progression and with a poor prognosis in breast cancer. In breast cancer cells, forced expression ofH19promotes DNA damage repair and resistance to PARP inhibition, whereasH19depletion diminishes DNA damage repair and increases sensitivity to PARP inhibitors.H19exerted its functional roles via direct interaction with ILF2 in the cell nucleus.H19and ILF2 increased BRCA1 stability via the ubiquitin-proteasome proteolytic pathway via theH19- and ILF2-regulated BRCA1 ubiquitin ligases HUWE1 and UBE2T. In summary, this study has identified a novel mechanism to promote BRCA1-deficiency in breast cancer cells. Therefore, targeting theH19/ILF2/BRCA1 axis might modulate therapeutic approaches in breast cancer.