Objective To investigate the effect of ganoderic acid A(GA-A) on apoptosis, invasion and KDR expression of human U251 cells. Methods Ganoderic acid A(GA-A) was prepared, human U251 cells were treated with 0.1, and 0.5 mmol/L GA-A, and the experiment was divided into blank control, low concentration and high concentration group. The expressions of KDR mRNA and KDR protein was assayed by RT-PCR and Western blot.The effect of GA-A on the proliferation and invasion capability of U251 cells was determined by CCK-8 and transwell assay in vitro, respectively. Flow cytometry was used to detect the influence of GA-A on the cell cycle and apoptosis of U251 cells, and TUNEL staining was detected the cell apoptosis too. Results Compared with the control group, KDR mRNA and protein expression of high concentration and low concentration group were significantly decreased(P < 0.05), GA-A can significantly reduce the cell growth rate, reduce the proportion of cells in G1 phase and increase the proportion of S phase and G2/M phase, cells apoptosis was significantly increased in the high concentration and low concentration group (P < 0.01), and cells proliferation and invasion was significantly decreased (P < 0.05). Compared with low concentration group, the high concentration group induce cell apoptosis and inhibit the expression of KDR more significant (P < 0.05). Conclusions Ganoderma acid A can induce apoptosis in U251 cells, inhibit proliferation and invasion, and can inhibit the expression of KDR mRNA and protein, which may be one of the mechanisms of anti-tumor.