Abstract: Objective: To discuss the function and potential mechanism of apigenin on renal carcinoma cells. Methods: Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) was applied to find potential action targets of apigenin. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was applied to analyzed the pathway enrichment of potential targets. Human renal carcinoma 786- 0 cells were treated with different concentrations of apigenin. CCK8 assay was used to measure the effect of apigenin on the proliferation of human renal carcinoma 786-0 cells. The effect of apigenin on 786-0 cell cycle was detected by flow cytometry. The protein expression of protein kinase B(Akt) and phosphorylated protein kinase B(p-Akt) of the cells was detected by Western blot,and the effect of apigenin on the tumor was verified by using nude mouse model with solid tumors constructed from human renal carcinoma 786-0 cells. Results:A total of 82 potential targets of apigenin were screened out. Pathway enrichment analysis showed that there were 102 eligible pathways, most of which were closely related to tumors, including renal carcinoma, cell cycle and phosphatidylinositol kinase(PI3K)/Akt pathway. After the intervention of 786-0 cells with different concentrations of apigenin,compared with the 0 μmol/L group,the inhibition rate of cell proliferation was increased in the 10 μmol/L group, the 20 μmol/L group and the 40 μmol/L group(P<0.05, P<0.01); the proportion of cells in G1 phase and the expression of p-Akt protein were decreased in the 20 μmol/L group and the 40 μmol/L group(P<0.05),and the proportion of cells in G2 phase was increased(P<0.05);the proportion of cells in S phase was decreased in the 40 μmol/L group(P<0.05). The results of animal experiments showed that compared with the control group,the tumor volume of nude mouse in the experimental group was significantly reduced on the 12th,15th and 18th days(P<0.05). Conclusion:Network pharmacology, cell experiment and animal experiment have indicated that apigenin may inhibit the cell proliferation of renal clear cell carcinoma by regulating the PI3K/Akt pathway.