Abstract: Objective :To investigate the expression of p21WAF1 cyclinDl CDI4 and their relationship in pancreatic cancer. Methods :Immunohistochemical detector with new second generationaltow steps method was used detect the expression of p21WAF1 cyclinDl CD in 48 cases of pancreatic cancer and 14 cases of chronic pancreatitis. Results :The expression of p21WAF1 cyclinDl CD proteins in pancreatic cancer were 52.08% (25/48) 70.85% (34/48) and 62.50% (30/48), respectively. The p21WAF1 proteins was luced in pancreatic cancer (P<0.01), while the cyclinDl and CD proteins were increased (P<0.01), as compared that in chronic pancreatitis. The positive rates of p21WAF1 in the pancreatic cancer, with well lifFerentiation, non-metastatasis and clinical stage fl,was significantly higher than that in the cases with poor differentiation, metastasis and clinical stage (P<0.01), and that of cyclinDl and CD were opposite (P<0.05). The negative correlation was found between the expression of p21WAF1 and cyclinDl CD (r=-0.340, P<0.05; r=-0.571, P<0.01).The positive correlation was also found between cyclinDl and CD (r=0.450, P<0.01). Conclusions :The loss of p21WAF1 expression and overexpressions of cyclinDl and CD may contribute the pathogenesis of pancreatic cancer. These proteins play a critical role in cell cycle arrest through p21WAF1/cyclinDl/CDK4 pathway.