A major production constraint of lilies is gray mold caused by the necrotrophic fungus Botrytis elliptica. The molecular basis of lily plant resistance to B. elliptica remains largely unexplored. To systematically dissect transcriptomic responses, we constructed four RNA-seq libraries from the leaves of Lilium regale, a promising Chinese wild Lilium species, after B. elliptica infection for 0, 4, 12, or 24 h. The sequence reads were assembled into 96 416 unigenes, of which 7697 were differentially expressed. Profiling analysis revealed changes in gene expression, including 2261 downregulated genes and 3599 upregulated genes. Quantitative real-time polymerase chain reaction analysis of 39 defense-related unigenes confirmed that the transcriptional changes of these genes presented in the RNA-seq data were predominately affected by B. elliptica infection. Key B. elliptica modulated genes played roles in defense responses mediated by phytohormones involved in jasmonate signaling, whereas salicylic acid and ethylene were not involved. Among transcription factors, some WRKYs, MYB, and ethylene responsive factor were clearly upregulated. Additionally, a group of genes encoding known important defense-related proteins, such as receptor-like kinases, antioxidant enzymes, polyphenol oxidase, pathogenesis-related proteins, and proteins associated with phenylpropanoid metabolism, exhibited high transcript abundances. Furthermore, the expressions of selected candidate genes were induced more rapidly and strongly in the resistant genotype than in the susceptible genotype. Taken together, the results provide a better understanding of the defense responses involved in the crosstalk between the lily and B. elliptica and a valuable set of sequence data for gray mold resistant candidate gene discovery.