A phenanthroindolizidine glycoside 6-O-beta-D-glucopyranosyl-tylophorinidine (1), the first glycoside of phenanthroindolizidine alkaloid in nature, was isolated from whole plants of Tylophora atrofolliculata (Asclepiadaceae). Its structure was elucidated by means of spectral and chemical evidences. Compound 1 showed potent inhibitory effect (IC50 : 69 +/- 13 nM) on hypoxia induced factor-1 (HIF-1) activation. It was discovered that glucosylation at C-6 of 1 could lead to reduction in cytotoxicity against normal cells and enhance its selectivity in tumor cells inhibition.