The aim of this study was to examine the softening mechanism of Jiashi melon during postharvest storage， and assess differences in the expression of genes involved in fruit softening under different storage conditions. RNA-sequencing was employed to characterize the transcriptomic profiles of Jiashi melon that were stored at 21， 3 ℃ and 0.5 ℃ for 0， 12， 24 d. A total of 118 softening-related genes were obtained. Among these genes， 68 genes presented opposite expression pattern between 3 ℃ and 21 ℃， and 69 genes presented opposite expression pattern between 0.5 ℃ and 21 ℃. At a storage time of 12 d， 10 common differentially expressed genes (DEGs) were obtained among 21 ℃-3 ℃， 21 ℃-0.5 ℃， and 3 ℃-0.5 ℃ groups. Relatively， at a storage time of 24 d， 17 common DEGs were obtained among 21 ℃-3 ℃， 21 ℃-0.5 ℃， and 3 ℃-0.5 ℃ groups. The key genes that played an important regulatory role in the softening process have been screened and verified by qRT-PCR. The results showed that the softening was delayed at low temperatures by regulating the expression of key softening-related genes. The results provide a theoretical basis for further studies on the softening mechanism and preservation of Jiashi melon.