A simple, efficient and environmental friendly method was proposed for determining five sesquiterpenoids of Curcuma wenyujin by MSPD extraction coupled with MEEKC separation. Molecular sieve was applied as a solid support for extraction of sesquiterpenoids for the first time. Various parameters affecting extraction and separation efficiency were investigated. The optimized conditions involved dispersing sample (200mg) with 200mg of TS-1 for 150s and using 1000L of methanol to elute five target analytes. Finally, they were well separated by using a running buffer containing 1.3% SDS, 5.0% 1-butanol, 0.5% ethyl acetate and 10% acetonitrile in 10mM borate buffer at pH 9.0. Consequently, the developed method was fully validated and successfully applied to determine the five sesquiterpenoids including curdine, curcumenol, germacrone, furanodiene and -elemene in Curcuma wenyujin origin's Chinese herbal medicines. Furthermore, hierarchical cluster analysis was performed based on the contents of target compounds for distinguishing steamed and non-steamed drugs. The present study provided a promising method for fast investigation and discrimination of chemical difference in steam & non-steamed Chinese medicines from Curcuma wenyujin origin.