Objective: To investigate the influence of heat shock protein (HSP70) knock down on the growth of colon cancer cells in nude mice. Methods: Two shRNA plasmid vectors against HSP70 (HSP70 shRNA-1 and HSP70 shRNA-2) were constructed and were transfected into colon cancer HT29 cells respectively, and the empty plasmid transfected (negative control) and untransfected HT29 cells (blank control) served as control. The gene and protein expressions of HSP70 in the cells of each group were determined by RT-PCR and Western blot analysis, respectively. Three groups of xenograft tumor model in nude mice were created by subcutaneous inoculation with HSP70 shRNA-2 transfected, empty plasmid transfected and untransfected HT29 cells respectively, and then the growth of the xenograft tumors was observed. The lumps in the nude mice were stripped off after three weeks and the H&E, immunohistochemical staining and TUNEL assay were performed to determine the morphological condition, proliferating cell nuclear antigen (PCNA) expression and apoptosis in the tumor tissues, respectively. Results: The results of RT-PCR and Western blot showed that the gene and protein expressions of HSP70 in HT29 cells were significantly inhibited by either HSP70 shRNA-1 or HSP70 shRNA-2 transfection, which was more evident in HSP70 shRNA-2 transfected cells. Compared with blank control group, in HSP70 shRNA-2 transfection group, the growth of the xenograft tumor was significantly reduced (P<0.01), marked necrosis in the central area of the tumor was observed, the PCNA expression significantly decreased and apoptosis significantly increased in the tumor tissues (P<0.01), while none of the obvious above changes were noted in empty plasmid transfection group. Conclusion: HSP70 silencing can inhibit the growth and enhance the apoptosis of xenograft tumor of colon cancer HT29 cells in nude mice. HSP70 is probably an effective target for colon cancer.