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Background: Fusarium wilt disease is leading threat to watermelon yield and quality. Different cultivation cropping systems have been reported as safe and efficient methods to control watermelon Fusarium wilt. However, the role of salicylic acid (SA) in watermelon resistance to Fusarium wilt in these different cultivation systems remains unknown. Methods: in this experiment, we used RNA-seq and qRT-PCR to study the effect of SA biosynthesis on improving watermelon health, demonstrating how it may be responsible for Fusarium wilt resistance under continuous monocropping and oilseed rape rotation systems. Results: the results revealed that the expression of the CIPALs genes was key to SA accumulation in watermelon roots. We observed that the NPR family genes may play different roles in responding to the SA signal. Differentially expressed NPRs and WRKYs may interact with other phytohormones, leading to the amelioration of watermelon Fusarium wilt. Conclusions: further understanding of gene expression patterns will pave the way for interventions that effectively control the disease.