OBJECTIVE： To study the effect and mechanism of physcion 8-O-β-glucopyranoside （PG） on the apoptosis of skin melanoma A375 cells. METHODS： After A375 cells were treated by PG with 0， 10， 20， 50 μg/mL for 24， 48， 72 h， CCK-8 method was adopted to determine the survival rate of cells. After A375 cells were treated by PG with 0 （control）， 20， 50 μg/mL for 48 h， flow cytometry was used to detect the apoptosis rate of cells with membrane protein Ⅴ/propidium iodide （PI） double staining. Immunoblotting was used to detect the protein expressions of Caspase-3 and polyadenyl adenine diphosphate ribose polymerase （PARP） and protein expressions of cytochrome C inside and outside mitochondria. After A375 cells were treated by PG with 0 （control）， 5， 10 μmol/L for 48 h， enzyme substrate method was used to determine the activities of Caspase-8 and Caspase-9. RESULTS： PG can effectively decrease the survival rate of A375 cells. Compared with control， apoptosis rate of cells was obviously increased after treated by PG with 20， 50 μg/mL （P＜0.01）； protein expressions of Caspase-3， PARP in cells and cytochrome C in cell matrix were obviously enhanced （P＜0.05 or P＜0.01）； and protein expression of cytochrome C in mitochondria was obviously weakened （P＜0.05 or P＜0.01）. Caspase-9 activity in cells was obviously enhanced after treated by PG with 5， 10  μmol/L （P＜0.05 or P＜0.01）； and Caspase-8 activity had no obvious changes. CONCLUSIONS： PG can inhibit activity of A375 cells and promote its apoptosis， and its pro-apoptotic effects is achieved by destructing mitochondrial membrane potential and promoting cytochrome C outflow.