show Abstracthide AbstractMelon (Cucumis melo L), is an economically important vegetable crop, is native to tropical and southern Africa. Cold stress is one of the important environmental stresses affecting the yield of melon. To investigate the molecular mechanism of chilling tolerance in X207, we used Illumina sequencing technology based comparative transcriptome profiling analyses for both cold-sensitive M4-117 and cold-tolerant X207 subjected to the cold stress for 0, 8 and 72 h. The results showed that 1277 and 2393 differentially expressed genes (DEGs) were identified for 8 and 72 h of chilling stress respectively in X207, while 1571 and 3761 DEGs were identified respectively in M4-117. A total 5633 DEGs were identified by GO classification and KEGG pathway analysis in both X207 and M4-117, revealed that most of them belong to signal transduction, transcription factors and metabolism, etc. Moreover, 13 DEGs were selected and further confirmed by quantitative real time PCR (qRT-PCR), which indicated significant differences in the expression of key genes in response to cold stress between cold-sensitive M4-117 and cold-tolerant X207. The new insight was provided in the molecular basis of melon responses to cold stress.