Watermelon fusarium wilt caused by Fusarium oxysporum f.sp. niveum (FON) is a destructive soil-borne disease throughout the world leading to serious economic losses and limit watermelon production. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to benzoic acid analogues. In this study, the median effective concentration (EC₅₀) values for cuminic acid in inhibiting mycelial growth of FON was 22.53μg/mL. After treatment with cuminic acid, mycelial morphology was seriously influenced; cell membrane permeability and glycerol content were increased markedly, but pigment and mycotoxin (mainly fusaric acid) were significantly decreased. Synthesis genes of bikaverin and fusaric acid both were down regulated compared with the control confirmed by quantitative RT-PCR. In greenhouse experiments, cuminic acid at all concentrations displayed significant bioactivities against FON. Importantly, significant enhancement of activities of SOD, POD, CAT and decrease of MDA content after cuminic acid treatment in watermelon leaves were observed in vivo. These indicated that cuminic acid not only showed high antifungal activity, but also could enhance the self-defense system of the host plant. Above all, cuminic acid showed the potential as a biofungicide to control FON.