Abstract: Objective To investigate the effect of tumor necrosis factor -related weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) on the proliferation and growth of pancreatic cancer. Methods Human pancreatic cancer (50 cases), chronic pancreatitis (40 cases) and normal pancreatic tissues (30 cases) were collected in West China Hospital from January 2012 to December 2013. TWEAK and Fn14 expressions in these tissues were checked with hematoxylin-eosin (HE) staining and immunohistochemistry method. Relationship between TWEAK expression and clinicopathological features of pancreatic cancer was analyzed. Results TWEAK expression rate was 36% (18/50) in pancreatic cancer, higher than that in chronic pancreatitis (17.5%, 7/40) and normal pancreatic tissues (13.3%, 4/30) ( P<0.05) .Expression intensity of TWEAK in three groups was also obviously ( P<0.05). The expression rate of Fn14 was 4.0% in pancreatic cancer ,7.0% in normal pancreatic tissues ,and 0% in chronic pancreatitis. TWEAK positive expression rate and high expression rate in pancreatic cancer were higher in IIB group ( P<0.05). Pathological grade was not related to TWEAK expression. Conclusion TWEAK/Fn14 involved in the progression of pancreatic cancer. In the tissue of pancreatic cancer, TWEAK was highly expressed, and Fn14 was lowly expressed.