Asarum sieboldii Miq., a perennial herb in the family Aristolochiaceae, is widely used to treat colds, fever, headache and toothache in China. However, little is known about the drought-tolerance characteristics of A. sieboldii. In this study, to elucidate the molecular–genetic mechanisms of drought-stress tolerance of A. sieboldii, RNA-seq was conducted. In total, 53,344 unigenes were assembled, and 28,715 unigenes were annotated. A total of 6444 differential-expression unigenes (DEGs) were found, which were mainly enriched in phenylpropanoid, starch and sucrose metabolic pathways. Drought stress revealed significant up-regulation of the unigenes encoding PAL, C4H, HCT, C3H, CCR and IGS in the methyleugenol-biosynthesis pathway. Under the condition of maintaining drought for 15 days and 30 days, drought stress reduced the biosynthesis of volatile oil by 24% and 38%, respectively, while the production of key medicinal ingredients (such as methyl eugenol) was increased. These results provide valuable information about the diverse mechanisms of drought resistance in the A. sieboldii, and the changes in the expression of the genes involved in methyleugenol biosynthesis in response to drought stress.