Melon wilt disease, also known as wilt disease, occurs from the seedling stage to the adult stage of plants. According to previous research, grafting is an effective means to improve the resistance of melons and Solanaceae vegetables to soil borne diseases and pests. With the popularization of vegetable grafting, the demand for rootstocks has rapidly increased. Therefore, this experiment takes seven pumpkin hybrid combinations as the research object, studies the resistance of different hybrid combinations to wilt disease, selects pumpkin hybrid combination rootstocks with strong resistance, and provides reference for grafting cultivation in production. The research results indicate that 10 days after inoculation with pathogens, the overall plant infection in the early stage was not significantly affected by the pathogens, and there was no significant difference between the various hybrid combinations. On the 20th day of inoculation with pathogens, Yanbian-3×360-3 showed significant differences in plant height and chlorophyll indicators compared to other pumpkin rootstock hybrid combinations. On the 30th day of pathogen inoculation, Yanbian-3×360-3 showed significantly higher plant stem diameter indicators than other pumpkin rootstock hybrid combinations, showing significant differences from other pumpkin hybrid combinations. Therefore, it can be concluded that Yanbian-3×360-3 had the optimal relative growth rate. Moreover, on the 30th day of pathogen inoculation, the leaf disease index was 52.67%, and the stem disease index was 37.92%, indicating that Yanbian-3×360-3 was less affected by pathogen infection and has stronger resistance to wilt disease. On the 30th day after inoculation with pathogenic bacteria, the investigation showed that the disease index of leaves in Yanbian-2×041-1 was 54.67%, and the disease index of stem dissection was 45.83%. Hetoua2×041-1, with a leaf disease index of 95.33% and a stem cutting disease index of 87.92%. Among the seven pumpkin hybrid combinations, Yanbian-3×360-3 and Yanbian-2×041-1 have the best disease resistance and are neutral disease resistant combinations; Hetoua2×041-1 has the most severe incidence and is a highly susceptible combination. The two pumpkin rootstocks, Yanbian-3×360-3 and Yanbian-2×041-1, have good resistance to melon wilt disease and can be used as grafting rootstocks for melon wilt disease resistance. Considering the affinity between grafting rootstocks and scions and the impact on yield after grafting, further verification is needed in the later stage.