• The endophyte Bacillus velezensis SJ22 exhibits high antifungal activity. • Strain SJ22 represents a promising biocontrol agent for F. taipaiensis bulb rot. • Strain SJ22 induced systemic resistance in F. taipeiensis . Bulb rot in Fritillaria taipaiensis P. Y. Li, caused by Fusarium spp., is a destructive soil-borne disease that severely affects the yield and quality of F. taipaiensis . Chemical fungicides are currently the primary means of controlling this disease; however, their use poses risks to human health and the environment. Biological control is thus a preferable alternative to counteract the threats associated with pathogens. In this study, an endophytic bacterium, designated SJ22, was isolated from bulb tissue of F. taipaiensis , and it exhibited significant antagonism against Fusarium spp., with inhibition rates on plates ranging from 84.35% to 89.96% and a control rate of 73.38% in pot experiments. Morphological observations and phylogenetic analyses identified the isolate SJ22 as Bacillus velezensis . Furthermore, the antifungal mechanisms of SJ22 include the inhibition of spore germination, alteration of hyphal morphology, and disruption of cell membrane integrity. Its volatile organic compounds exhibited broad-spectrum antifungal activity in vitro , with an inhibition rate of 28.36% to 59.12%, and demonstrated significant control efficacy in vivo . Transcriptome analysis revealed that SJ22 induced systemic resistance in F. taipaiensis by upregulating defense-related genes, primarily through enhancing the phenylpropanoid biosynthesis pathway and promoting the salicylic acid/ethylene signaling pathway to induce the production of pathogenesis-related proteins and increase the activity of defense-related enzymes. In summary, we isolated an endophytic bacterium that exerts its biocontrol function through both inhibiting pathogen growth and inducing resistance.