Objective To investigate the expression and prognostic significance of CD151, c-Met and integrin alpha 3, alpha6 in pancreatic ductal adenocarcinoma (PDAC). Methods The expression of CD151, c-Met and integrin alpha3, alpha6 in 71 patients with PDAC and 10 samples of normal pancreas tissues were detected by immunohistochemistry, and the relationship between the expression of CD151, c-Met and integrin alpha 3, alpha 6 and the clinicopathological features, prognosis of these patients was analyzed. Results The positive expression rates of CD151, c-Met and integrin alpha 3, alpha 6 in PDAC were 81.69% (58/71) , 69.01% (49/71), 69.01% (49/71) and 84.51% (60/71) , and there was no expression in normal pancreas tissues. The expressions of CD151, c-Met were significantly associated with TNM stage and lymph node metastasis (P < 0.05). The expression of CD151 was positively correlated with the expressions of c-Met and integrin alpha3, alpha6 (r =0.583, P =0.000, r = 0.457;P =0.000, r = 0.671 ;P =0.000). Univariate analysis suggested the expression of CD151, c-Met and integrin alpha3, alpha6 was associated with survival (P<0.05). Multivariate analysis suggested the expression of CD151, c-Met was the independent prognostic factor for post-operative survival. Conclusions CD151, c-Met and integrin alpha3, alpha6 play a role in the development, metastasis and prognosis of PDAC, and they might be new markers to predict biological behavior and the prognosis of PDAC patients.