Objective To observe the expression of PUMA, P53, Bax and Bcl-2 protein in pancreatic ductal adenocarcinoma (PDA), and to investigate the role of PUMA in tumorigenesis of PDA and its relationship with P53, Bax and Bcl-2 protein expression. Methods The expression of PUMA, P53, Bax and Bcl-2 protein was examined by immunohistochemical EnVision method in 65 PDA tissues and the corresponding adjacent tissues. Results The positive rate of PUMA protein expression was 30.8%(20/65) in the PDA tissues, which was significantly lower than that in the corresponding adjacent tissues (49.2%\[32/65\], P<0.05). The expression of PUMA protein was significantly correlated with the tumor size and lymph node metastasis (P<0.05), but not with patient’s age, sex, tumor location, differentiation degree, tumor stage or neural invasion. PUMA expression was negatively correlated with P53 and Bcl-2 expression(P=0.019,P=0.015), but was not correlated with Bax expression in PDA tissues. Conclusion Decreased PUMA protein expression is correlated with tumor size and lymph node metastasis in PDA patients, suggesting that PUMA protein might be involved in the tumorigenesis and development of PDA. Detection of PUMA protein expression may be used for predicting the prognoses of PDA patients.