This research aimed to reveal the influence of rapeseed cake fertilizer application on soil nutrient supply，photosynthetic characteristics，yield and quality of muskmelon，and then to provide theoretical basis for improving the quality and efficiency of muskmelon production. Using“Xitian 208”muskmelon as test materials，five treatments were set up under the equal nutrient inputs conditions，including conventional fertilizer application(CK)，rapeseed cake fertilizer substitution of 10% chemical fertilizer application(T1)，rapeseed cake fertilizer substitution of 30% chemical fertilizer application(T2)，rapeseed cake fertilizer substitution of 50% chemical fertilizer application(T3)，rapeseed cake fertilizer substitution of 70% chemical fertilizer application(T4). The effects of different treatments on soil nutrient supply，soil enzyme activity，photosynthesis characteristics，yield and quality of muskmelon were studied and evaluated systematically. The results showed that，compared with fertilization application treatment，the application of rapeseed cake fertilizer significantly reduced the soil pH in melon root zone，increased the content of organic matter，alkali-hydrolyzed nitrogen，available phosphorus and available potassium，as well as the ratio of ammonium nitrogen to nitrate nitrogen，and then promoted the leaf photosynthesis. In addition，the application of rapeseed cake fertilizer significantly increased the activities of soil sucrase，soil alkaline protease，soil polyphenol oxidase and soil alkaline phosphatase，while reduced the activity of soil catalase. Principal component analysis results showed that the application of 30% and 50% rapeseed cake fertilizer exhibited the best effect on the yield and quality of muskmelon，in which yield were significantly increased by 3.59%-8.98%，soluble solids contents in the middle and edge were increased by 18.79%-19.69% and 26.30%-28.75%，respectively，Vc content were increased by 45.83%-49.24%，total soluble sugar content were increased by 17.31%-18.60% and sugar-acid ratio were increased by 29.64%-38.88%，while significantly reduced the accumulation of nitrate. No significant improvement for soil fertility，photosynthetic rate，yield and quality of muskmelon were observed when the proportion of rapeseed cake fertilizer reached 70%. Correlation analysis showed that the yield of muskmelon was positively correlated with alkali-hydrolyzed nitrogen，soil urease activity；the quality of muskmelon was positively correlated with soil organic matter，alkali-hydrolyzed nitrogen，available potassium，available phosphorus，ammonium nitrogen，and the activities of soil sucrase，alkaline phosphatase and alkaline protease activities. In conclusion，rational application of rapeseed cake fertilizer could activate available nutrients，improve the soil environment of muskmelon root zone，enhance the leaf photosynthesis，and thus increased the muskmelon yield and quality. The results could provide reference for improving the quality，yield and the sustainable cultivation of muskmelon in Yanliang district.