To explore the effect of the extract from Camellia oleifera cake on the postharvest disease resistance of pitaya, pitaya Zihonglong was sprayed with different concentrations of C. oleifera cake extract before harvest. The fruits were stored at (10±0.5)℃ and 90%-95% RH after harvest. The changes of physical and chemical properties, nutritional components, reactive oxygen species (ROS) metabolism and defense-related enzyme activities of pitaya fruits after harvest were analyzed, and the correlation between each index and comprehensively scores were analyzed. The results indicated that the preharvest spraying extract from C. oleifera cake could effectively reduce the decay index (DI) of pitaya fruit. The respiratory rate (RR) and ethylene release rate (ERR) of pitaya fruit were effectively inhibited by C. oleifera cake extract at the later storage period. Pitaya fruit treated with C. oleifera cake extract effectively delayed the decrease of ascorbic acid (AsA) content, and increased the activities of catalase (CAT), superoxide dismutase (SOD) and other antioxidant enzymes, effectively promoted the metabolism of hydrogen peroxide (H₂O₂) in fruit, reduced the H₂O₂ content, and effectively removed the ROS accumulation during the fruit physiological metabolism. Meanwhile, the C. oleifera cake extract effectively increased the activities of defense-related enzymes such as phenylalanine ammonialyase (PAL), peroxidase (POD), polyphenol oxidase (PPO), β-1,3-glucanase (GLU) and chitinase (CHI) in pitaya fruit, thus improving its disease resistance. Correlation analysis founded that pitaya fruit DI was closely related to the ROS accumulation and membrane lipid peroxidation. Decreasing oxidative stress and maintaining the integrity of cell membrane were the basis for improving the disease resistance of pitaya fruit, and enhancing the disease resistance of pitaya fruit was helpful to reduce decay. Comprehensive evaluation showed that the comprehensive score of pitaya fruit preharvest spraying with 1.00% C. oleifera cake extract was the highest, indicating that its treatment effect was the best. In conclusion, preharvest spraying with 1.00% C. oleifera cake extract could maintain quality of pitaya fruit by improving the antioxidant and disease resistance. The results provide a theoretical reference for the application of C. oleifera cake extract in the postharvest storage and preservation of pitaya.