This study is to explore the effects and mechanisms of nitrogen (N) reduction on the yield and quality of wax gourd and provide a scientific basis for the scientific reduction of chemical fertilizer for outdoor vegetables in Guangdong. A randomized block field plot experiment was conducted in Sanshui District of Foshan, Guangdong Province for two consecutive years with Tiezhu wax gourd under six treatments: CK, no nitrogen (N) fertilizer; T1, conventional fertilization; T2, N fertilizer reduced by 30%; T3, B and Mo fertilizers combined with N fertilizer reduced by 30%; T4, Ca and Mg fertilizers combined with N fertilizer reduced by 30%; T5, Ca, Mg, B and Mo fertilizers combined with N fertilizer reduced by 30%. The results show that wax gourd yield is decreased insignificantly by 8.76% under T2 compared with T1, and increased significantly by 21.3% and 32.2% (P<0.05) under T4 and T5 compared with T2, respectively, wax gourd yield under T5 is higher than T1. VC content in wax gourd is increased by 50.0% under T5 while its N content in wax gourd is decreased by 34.2% compared with T1. On the basis of reducing 30% N fertilizer, soil pH is significantly increased with application of Ca and Mg fertilizers, soil B content is increased significantly with the application of B and Mo fertilizers (P<0.05), the contents of Ca and Mo in wax gourd are higher in the treatments with medium and trace fertilizers than T2. In conclusion, in tropical South China, reducing N and applying medium and trace fertilizers can ensure the quality and yield of wax gourd, and combined application of medium and trace fertilizers has the best effect. The results provide a scientific basis for the scientific reduction of nitrogen fertizer application in open-field vegetables in Guangdong.