Abstract: Objective: To study the specific inhibition effect of short interfering RNAs(siRNA) on the mutant K-ras gene expression in PANC-1 cells. Methods: One pair of 63bp reverse repeated sequence targeting mutant K-ras^v12 mRNA were synthesized and inserted into plasmid pSilencer3.1 eukaryotic expression vector. After transfection into PANC-1 cells, the expression of K-ras gene was detected using RT-PCR and Western blot techniques. The effect of cell proliferation was studied by MTT test. Flow cytometry was used to detect the apoptosis of transfected cells. Results: The recombinant plasmid pSilencer3.1-K-ras^v12 was successfully constructed by the sequencing. The introduction of pSilencer3.1-K-ras^v12 was showed to efficiently and specifically inhibit the expression of K-ras^v12 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 inhibitory action on cell proliferation was confirmed by MTT test. The apoptotic rate of the pSilencer3.1-K-ras^v12 group was significantly higher than that of the control groups (P<0.05). Conclusion: The siRNA targeting mutant K-ras mRNA can specially suppress the expression of mutant K-ras gene in PANC-1 cells and it provides a new method and material to the biological therapy of cancer.