In the present study, we determined the importance of H19 lncRNA in breast cancer chemoresistance using doxorubicin as a model chemotherapeutic agent, and revealed for the first time that H19 lncRNA plays a leading role in breast cancer chemoresistance development, mediated mainly through a H19-CUL4A-ABCB1/MDR1 pathway. Here, H19 is linked to breast cancer.