Abstract: Objective To investigate the influence of suppressing Skp2 gene expression on growth of lung cancer xenografts and Skp2， p27， p21 protein expression in xenografts. Methods BALB／c nude mice were injected subcutaneously with SPC-A-1 cells transfected with Skp2 shRNA 1，Skp2 shRNA 2 and Skp2 shRNA HK to construct nude mice of lung cancer animal models. Time of tumor formation and volume of tumors were observed. The mice were sacrificed and xenografts tissues were taken, and tumor inhibition rate was caculated. Protein expression of Skp2，p27， p21 in xenografts tissues was detected by Western blotting method. Results Compared with the control group and Skp2 shRNA HK group， tumor growth were inhibited and tumor volume reduced significantly in Skp2 shRNA 1 and Skp2 shRNA 2 groups. Tumor inhibition rate of Skp2 shRNA 1 and Skp2 shRNA 2 groups were（69.2±5.6）％ and（64.5±6.1）％； expression of Skp2 protein were reduced（73.5±4.2）％， and（67.3±3.2）％； expression of p27 protein were increased（63.6± 2.2）％ and（57.3±2.4）％； expression of p21 protein were increased（54.6 ±3.4）％ and（51.7± 3.1）％. Conclusion Inhibiting the expression of Skp2 gene can significantly suppress the growth of transplanted tumor， Skp2 is expected to become a target for gene therapy of lung cancer in future.