Abstract:Fusarium wilt is a refractory soil-borne disease known as "cancer" in cucurbitaceous vegetables. It has become a bottleneck restricting the sustainable development of the cucurbitaceous vegetable industry in China. We briefed the negative impacts of Fusarium wilt on cucurbitaceous vegetables and introduced the damaging mechanism of Fusarium wilt from cell wall-degrading enzymes, toxins, signal transduction, and virulence genes. Furthermore, we innovatively elaborated on the mechanism by which rhizosphere microbiome in defending against Fusarium wilt of cucurbitaceous vegetables from the pathogen, soil, and plant perspectives. We then discussed the key factors associated with the occurrence and inhibition of Fusarium wilt. Finally, we prospected the construction of the core microbiome and the research on the molecular mechanism of rhizosphere microbiome. It is expected that the application of biocontrol microorganisms in the prevention and control of diseases will enter a new era. This work can provide ideas for deciphering the mechanism of improving crop resistance to diseases.