In the present study, we investigated the effect of Mesothelin sliencing or overexpression on human pancreatic cancer cell lines AsPC-1(p53-null), HPAC and Capan-2(wt-p53), Capan-1 and MIA PaCa-2 (mutant p53) in vivo, and discussed the mechanism. The gene discussed is TP53; the disease is pancreatic neoplasm.