A series of dihydroartemisinin derivatives was synthesized, and their anti-proliferation activity against cancer cells was evaluated. Structure-activity relationship studies led to the discovery of dihydroartemisinin-bile acid conjugates that exhibit broad-spectrum anti-proliferation activities. Among them, the dihydroartemisinin-ursodeoxycholic acid conjugate (49) was the most potent, with IC<sub>50</sub> values between 0.04 and 0.96 μM when tested to determine its inhibitory properties against 15 various cancer cell lines. In vivo experiments showed that compound 49 effectively suppressed tumor growth in an A549 cell xenograft model at the dosage of 10 mg/kg body weight and in Lewis lung cancer cell transplant model at the dosage of 12 mg/kg body weight.