Abstract: 【Objective】 Orobanche aegyptiaca is a completely parasitic, malignant weed. Bacillus velezensis JTB8-2 demonstrates potent inhibitory capabilities against O. aegyptiaca. Investigating its mechanism, so research into it might provide a solid theoretical foundation for the application of this strain in the field. 【Methods】 In order to investigate the molecular mechanism of B. elezensis JTB8-2-induced resistance to O. aegyptiaca in tomato, we employed pot culture, enzyme activity assays, and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MRM-MS/MS). 【Results】 The findings revealed that the application of B. elezensis JTB8-2 fermentation broth to tomatoes at 20, 30, and 40 days after transplantation resulted in a parasitic O. aegyptiaca tubercle count of 0.33, 0.17, and 0.33, respectively. This represented a reduction of 81.67%, 96.96%, and 95.54% compared to the control group, and a reduction of 50.75%, 79.52%, and 50.75%, respectively, compared to the NB medium treatment. The catalase (CAT) activity of tomato roots was found to be higher than that of both the medium treatment and water control group after 3, 20, and 30 days. Moreover, differences were observed in the content of 11 metabolites among 28 plant hormone metabolites in tomato roots. The levels of cytokinins and auxin compounds in tomato roots treated with strain JTB8-2 were higher than those in the water control group. 【Conclusion】 The upregulation of catalase activity, cytokinin, and auxin-related hormones in tomato roots treated with strain JTB8-2 may elicit a systemic resistance response in the plant, thereby reducing the severity of O. aegyptiaca parasitism.