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Background: Botrytis cinerea, the causal agent of gray mold has a great economic impact on several important crops. This necrotrophic fungus causes disease symptoms during vegetative growth and also into postharvest stages. The current method to combat this disease is fungicide application, with high economic costs and environmentally unsustainable impacts. Moreover, there is an increasing general public health concern about these strategies of crop protection. We studied the protection of tomato plants against B. cinerea by previous root treatment with menadione sodium bisulfite (MSB), a known plant defense activator., Results: Root treatment 48 h before inoculation with MSB 0.6 mmol L -1 reduced leaf lesion diameter by 30% and notably cell deaths, compared to control plants 72 h after inoculation. We studied the expression level of several pathogenesis-related (PR) genes from different defense transduction pathways, and found that MSB primes higher PR1 expression against B. cinerea. However, this stronger induced resistance was impaired in transgenic salicylic acid-deficient NahG line. Additionally, in the absence of pathogen challenge, MSB increased tomato plant growth by 28% after 10 days. Our data provide evidence that MSB protects tomato plants against B. cinerea by priming defense responses through the salicylic acid (SA)-dependent signaling pathway and reducing oxidative stress., Conclusion: This work confirms the efficacy of MSB as plant defense activator against B. cinerea and presents a novel alternative to combat gray mold in important crops., (© 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)