Abstract: 【Objective】 To investigate the inhibitory impact of hypobaric treatment combined with NO fumigation on the postharvest senescence of cantaloupe. 【Methods】 The Xinjiang characteristic variety, Xizhoumi 17 was chosen as the experimental material. A concentration of 60 μL/L of NO was used for fumigation treatment under pressure of 20 KPa. The postharvest quality and enzyme activities associated with reactive oxygen species metabolism (ROS) were analyzed, aiming to explore the relationship between fruit senescence progression and ROS metabolism. 【Results】 The fumigation treatment of 20 KPa + 60 μL/L NO was the most suitable fumigation method, which effectively delayed the decrease of fruit firmness; reduced the weight loss and decay rate of fruit; delayed the decrease of fruit soluble solids and titratable acid; significantly inhibited the increase of respiration intensity, conductivity and malondialdehyde; maintained the activities of peroxidase (POD), catalase (CAT) and superoxide dismutase (SOD) (67.36%, 69.96%, 34.34%), and consequently maintained the scavenging capacity of superoxide anion and hydrogen peroxide (SOD) activities (67.36%, 69.96%, and 34.34%), which in turn maintained the scavenging capacity of superoxide anion and hydrogen peroxide. 【Conclusion】 Hypobaric treatment combined with NO fumigation effectively enhances the activities of antioxidant enzymes and alleviate the accumulation of reactive oxygen species in cantaloupe. This reduction in oxidative damage prolonged the postharvest quality and preservation of the fruit.