The cultivation and production of passion fruit (Passiflora edulis) are severely affected by viral disease. Yet there have been few studies of the molecular response of passion fruit to virus attack. In the present study, RNA-based transcriptional profiling (RNA-seq) was used to identify the gene expression profiles in yellow passion fruit (Passiflora edulis f. flavicarpa) leaves following inoculation with cucumber mosaic virus (CMV). Six RNA-seq libraries were constructed comprising a total of 42.23 Gb clean data. 1,545 differentially expressed genes (DEGs) were obtained (701 upregulated and 884 downregulated). Gene annotation analyses revealed that genes associated with plant hormone signal transduction, transcription factors, protein ubiquitination, detoxification, phenylpropanoid biosynthesis, photosynthesis and chlorophyll metabolism were significantly affected by CMV infection. The represented genes activated by CMV infection corresponded to transcription factors WRKY family, NAC family, protein ubiquitination and peroxidase. Several DEGs encoding protein TIFY, pathogenesis-related proteins, and RNA-dependent RNA polymerases also were upregualted by CMV infection. Overall, the information obtained in this study enriched the resources available for research into the molecular-genetic mechanisms of the passion fruit/CMV interaction, and might provide a theoretical basis for the prevention and management of passion fruit viral disease in the field.