Abstract: Continuous mono-cropping is the major factor that restricted the development of watermelon plantation. Application of bio-organic fertilizer (BOF) target for watermelon fusarium wilt disease (FWD) can provide an environment-friendly way to reduce FWD problem. In this experiment, nursery application of the BOF was used to control Fusarium oxysporum f. sp. niveum. Results showed: 1) the best controlling effect was found in the treatment of BOF in nursery application plus the second application in transplanted soil, where the wilt disease incidence was 0% comparing to 100% in control. 2) After the application of BOF, Fusarium oxysporum number was kept below 104cfu/g both in rhizoplane and in the bulk soil. Fusarium oxysporum number was significantly lower than control（1.17×104cfu/g in the rhizoplane soil and 1.1×104cfu/g in the bulk soil, respectively). 3) Biomass was significantly increased with 1% BOF treatment 17 days after sowing in nursery pot comparing with control. With 1% BOF treatment, the fresh-weight of root biomass increased 73.3%, dry-weight increased 66.7%, while the fresh-weight of above ground biomass increased 56.7% and dry-weight increased 41.9%. During 67 day experiment period, biomass with BOF treatment (15.97±0.58 g/plant, DW) was significantly higher than that of the control (8.73±0.35 g/plant, DW), and was about 1.83 fold higher than control. Results suggested that BOF application both on nursery application and second application in culture pot can effectively prevent watermelon Fusarium wilt disease occurrence; promote watermelon plant growth, and easecontinuous mono-cropping obstacles.