OBJECTIVE： To explore the effects and mechanism of extracts， active constituents and constituent combination of Sinopodophylli Fructus on cell proliferation of human breast cancer. METHODS： Acid phosphatase method was conducted to determine the effects of 4 extracts [ethanol extract （Xc）， petroleum ether extract from ethanol extract （Xp）， ethyl acetate extract from ethanol extract （Xe）， n-butanol extract from ethanol extract （Xz）]， 5 active constituents [podophyllotoxin （S1）， deoxypodophyllotoxin （S2）， 4-desmethyl deoxypodophyllotoxin （S3）， 8-isopentenyl kaempferol （S4）， 8，2′ -diisoprenyl quercetin-3-methyl ether （S5）] and 3 active constituent combination [combination 1， S1-S2-S3-S4-S5 （2 ∶ 4 ∶ 1 ∶ 4 ∶ 32）， Z1； combination 2， S2-S4 （1 ∶ 1）， Z2； combination 3， S3-S4 （1 ∶ 4）， Z3] on the MDA-MB-231， MCF-7 cell proliferation； flow cytometry was adopted to detect the effects of above-mentioned samples on MDA-MB-231， MCF-7 （T47D） cell cycle and mitochondrial membrane potential. RESULTS： The active constituent combination Z1 showed significant inhibitory effects on MDA-MB-231， MCF-7 cells， the half inhibitory concentrations （IC50） were （0.27±0.2）， （0.11±0.1） μg/mL； extracts Xc， Xp， Xe， active constituents S2， S4 and active constituent combination Z2， Z3 showed relatively strong inhibitory effects on MDA-MB-231， MCF-7 （T47D） cell proliferation （IC50＜15 μg/mL）. Both extracts and active constituents can block MDA-MB-231， MCF-7 cell cycle in G2/M phase； all active constituents can block MDA-MB-231， T47D cell cycle in G0/G1 phase， and can reduce MDA-MB-231， T47D cell mitochondrial membrane potential. CONCLUSIONS： The active constituents and constituent combination of Sinopodophylli Fructus can inhibit cell proliferation of breast cancer by affecting cell cycle and mitochondrial membrane potential.