In order to explore the inhibitory effects of leaf flavonoids in different cultivars of fig (Ficus carica L.) from different harvesting periods on cancer cell proliferation,leaves of three cultivars of fig were harvested from July to November,respectively,to extract the total flavonoids and evaluate their inhibitory rates on different cancer cell lines.Then,the flavonoids from ‘Brunswick’ fig leaves harvested in August were further chose to elucidate the cellular and molecular mechanisms behind its inhibitory effect on the proliferation of human gastric cancer SGC-7901 cells by flow cytometer and qRT-PCR technique.Finally,the components of flavonoids in fig leaves were qualitatively and quantitatively analyzed with LC-MS/MS to select candidate species highly related to anti-cancer activity and provide theoretical basis for identification of anti-cancer components of fig flavonoids.Results showed that:the inhibitory rate of flavonoids in ‘Brunswick’ leaves on tested cancer lines was significantly higher than that in ‘Masui Dauphine’ and ‘Bojihong’.Among all harvesting dates,the leaves harvested in August showed the higher inhibitory effect on tested cancer lines,with the highest inhibitory rate of 86.65% on SGC-7901 gastric cancer cells.After treatment of the leaf flavonoids in ‘Brunswick’ leaves harvested in August,the cell apoptosis of SGC-7901 was accelerated,mitochondrial membrane potential decreased,and the cell division cycle was blocked at S phase.What’s more,the expressions of pro-apoptotic genes Bax and p53 and cell cycle regulating gene E1F2 were up-regulated,while that of the anti-apoptotic gene Bcl-2 and the cell cycle-related genes Cyclin D1 and CDKs were down-regulated.LC-MS/MS analysis showed that sixty species of flavonoids could be identified from fig leaves,among which narcissus,isoorientin,and morin were highly related to the anti-cancer activity of leaf flavonoids,therefore,could be selected as the potential anti-cancer active ingredient candidates.The results of this study provide a theoretical basis for the development and utilization of fig leaf flavonoids in anti-cancer medicine.