Abstract: Abstract: This study was to set up a new model for good quality and high yield evaluation of water-saving watermelon cultivation in the arid regions of northwest China. The coupling effects of water and fertilizers on plant growth, yield and fruit quality of watermelon under plastic film mulch using drip irrigation were studied in a field experiment. Nine treatments were designed including three irrigation amount levels (W1, 450 m3/hm2; W2, 900 m3/hm2; and W3, 1350 m3/hm2) and three fertilizer levels (F1, N 81.53 kg/hm2+ P2O5 33.43 kg/hm2+ K2O 101.09 kg/hm2; F2, N 163.05 kg/hm2+ P2O5 66.85 kg/hm2+ K2O 202.18 kg/hm2; and F3, N 244.58 kg/hm2+ P2O5 100.28 kg/hm2+ K2O 303.27 kg/hm2). The results indicated that at the same fertilizer level, plant height increased but stem diameter decreased with increasing irrigation quantity. Compared with the other treatments, F2W2 showed much higher chlorophyll content in each growth stage. In the seedling stage, treatments with increased supplying of water and fertilizer gave rise to increases in leaf net photosynthetic rate and transpiration rate, and the net photosynthetic rate and transpiration rate in leaf were not significantly different between F2W2 and the other treatments. After the flowering stage, F2W2 treatment revealed a relatively high photosynthesis (with no significant difference with F3W3) in leaves, leading to the highest fruit yield (which was 3.6% higher than F3W3) and the highest water use efficiency (35.73% higher than F3W3) at the end of the experiment. For the fruit quality, F2W1 treatment and F3W2 treatment showed the highest soluble sugar content and total vitamin C content (but no significant difference with F2W2), respectively. The F2W2 treatment revealed the best performance with high content of total soluble solids (TSS), soluble protein and lycopene in fruits as well as good sugar acid ratio and excellent taste. The supply of water and fertilizer in the F2W2 treatment could meet needs for the watermelon growth, making plant grow strongly (with high photosynthesis capability in leaves and good quality as well as high yield in fruits) by economical irrigation water use efficiency. So, the F2W2 treatment was recommended as the best combination of water and fertilizer for the production of watermelon under drip irrigation and plastic film mulch in the arid area of northwest China.