Bioassay-guided purification on the ethanolic extract of the roots of Euphorbia kansui Liou ex S.B.Ho (Euphorbiaceae) led to the isolation of one unreported ingenane-type (euphorksol A) and six unreported jatrophane-type (euphorksjats A-F) diterpenoids, together with twenty-five known diterpenoids. Their structures were elucidated based on extensive NMR analysis and high-resolution mass spectrometry. Euphorksol A is a rare example of an ingenane-type diterpenoid with a 6,7-expoxy fragment. All compounds were examined for cytotoxicity against adriamycin (Adr)-sensitive HepG-2 and Adr-resistant HepG-2/Adr cell lines, but none showed significant activity. Then, all isolates were evaluated for their ability to reverse multidrug resistance (MDR). 6β,7β-Epoxy-3β,4β,5β-trihydroxyl-20- deoxyingenol and 3,5,7,15-tetraacetoxy-9-nicotinoyloxy-14-oxojatropha-6(17),11-diene showed significant MDR reversal activity in HepG-2/Adr cells (reversal fold: RF = 186.4 and 143.8, respectively) versus the positive control verapamil (Ver, RF = 93.7). Euphorksol A and kansuinin B exhibited moderate MDR reversal activity (RF = 57.4 and 68.9, respectively). These compounds are the first ingenane-type diterpenoids reported to show MDR reversal activity, which will provide new insights toward the development of MDR regulatory agents.