Objective Mining sesquiterpene cyclase genes involved in the biosynthesis of the hepatoprotective guaiane-type compound, procurcumenol, from Curcuma longa, to lay a foundation for the efficient synthesis of such compounds using synthetic biology approaches. Methods Transcriptome data were collected from different tissues of Curcuma longa(main root, lateral root, leaf, and flower). The precursor content of procurcumenol in these tissues was quantified via HPLC, followed by correlation analysis with the transcriptome sequencing results. Results Zedoarondiol, the precursor compound of procurcumenol, exhibited the highest content in main roots, followed by lateral roots, while it was not detected in flower and leaf samples. Under acidic conditions, zedoarondiol can undergo a dehydration reaction to be converted into procurcumenol. Through the combination of BLAST alignment, phylogenetic analysis, and multiple sequence alignment, 7 potential candidate genes encoding guaiane-type sesquiterpene cyclases were initially screened out from Curcuma longa L. Conclusion The expression levels of candidate genes were inconsistent with the distribution trend of zedoarondiol content in various tissues. The sesquiterpene cyclase genes involved in zedoarondiol biosynthesis in Curcuma longa L. may exhibit a spatiotemporal-specific expression pattern. This suggests that guaiane-type sesquiterpenes are cyclized in other tissues and then transported to the roots for subsequent steps such as oxidative modification. Given that procurcumenol can be prepared from its precursor zedoarondiol via acid-catalyzed dehydration reaction, increasing the yield of zedoarondiol can provide raw material support for the preparation of procurcumenol.