Abstract: Objective To study the inhibition effect of small interfering RNAs(siRNA) on the High Mobility Group Box-1 gene expression in PC-3 cells, and to study the inhibitory effect on invasion and metabasis of PC-3. Method First to construct eukaryotic expression vector carrying Pgenesil-1/HMGB1siRNA，then the vector was transfected into PC-3 and the positive colonise were screened by G418. The HMGB1 expression of PC-3 cells before and after transfection was detected by RT-PCR and Western blot. The abilities of migration and invasion were examined by scratch method, transwell and gel zymography. Results The recombinant plasmid Pgenesil-1/HMGB1siRNA was successfully constructed. The introduction of Pgenesil-1/HMGB1siRNA was showed to efficiently and specifically inhibit the expression of HMGB1 gene according to the results of RT-PCR and Western blot, and there was a significant difference between the siRNA transfected group and the control groups (P＜0.05). The migration and invasion of the Pgenesil-1/HMGB1 siRNA group was significantly lower than that of the control groups(P＜0.05). Conclusion Pgenesil-1/HMGB1siRNA can specially suppress the expression of HMGB1 gene in PC-3 cells and effectively inhibit the migration and invasion of PC-3 and it provides a new method and material to the biological therapy of cancer.