PERIOD1 (PER1) is a clock gene. We examined the effect of knockdown of PER1 on apoptosis in pancreatic cancer (MIA PaCa-2 and PANC-1) and hepatocellular carcinoma (HepG2) cells. Transfection of siRNA against PER1 into these cells increased the cleaved forms of caspases and poly-ADP-ribose-polymerase and induced apoptosis in all three cell lines. In the two pancreatic cancer cell lines, PER1 knockdown resulted in upregulation of Bax and downregulation of Bcl-2. Expression of p53 was not altered in the two pancreatic cancer cell lines containing mutated p53, but was upregulated in the HepG2 cells containing wild-type p53. Cell proliferation of MIA PaCa-2 and HepG2 was inhibited by PER1 knockdown. We also examined, by immunohistochemical staining, the expression of PER1 in pancreatic cancer tissue and found that PER1 was strongly expressed in pancreatic cancer cells. These results indicate that PER1 acts as an anti-apoptotic factor in pancreatic cancer cells.