Abstract: Watermelon is an important horticultural crop worldwide, but there are many diseases in it’s production. For the narrow genetic base, watermelon conventional breeding for disease resistance has been slow. In this paper, watermelon resistance gene cloning, establishment and optimization of tissue culture and genetic transformation system, commonly used transgenic methods, types of target genes into transgenic plants' performance and the safety of genetically modified watermelon research progress were summarized. Some problems in this field, which would be investigated further, were also pointed out and discussed. These conclusions will contribute to genetic engineering application in improving watermelon disease resistance.