Objective This study aimed to elucidate the mechanism of aerobic glycolysis regulating doxorubicin resistance in breast cancer. Methods Bioinformatics analyzed the expression and correlation of HJURP and FOXM1 in breast cancer tissues, and analyzed the enrichment pathway of HJURP. The expression of HJURP and FOXM1 in breast cancer cells and doxorubicin resistant cells were detected by qPCR. The binding relationship between FOXM1 and HJURP was verified by double Luciferase experiment and ChIP experiment. CCK-8 was used to detect cell viability and IC50 values. Western blot was used to detect the expression of specific genes related to glycolytic metabolic pathways. Seahorse XP96 analyzed the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of different treatment groups, and the assay kit detected the levels of pyruvate, lactate, and ATP in cells of each treatment group. Results HJURP was highly expressed in breast cancer and enriched in glycolysis pathway. Cell function experiments had found that HJURP could promote cell resistance to doxorubicin by regulating aerobic glycolysis. In addition, FOXM1 targets HJURP and was highly expressed in breast cancer, which was positively correlated with HJURP. In response experiment, HJURP overexpression could reverse the inhibition of FOXM1 knockdown on doxorubicin resistance in breast cancer cells. Conclusion The results of this study demonstrate that the transcription factor FOXM1 can activate the transcriptional regulation of HJURP aerobic glycolysis to promote doxorubicin resistance in breast cancer cells