Background: AHNAK nucleoprotein 2 (AHNAK2) belongs to the AHNAK protein family. The studies of AHNAK2 are limited. A recent study reported that AHNAK2 might be a biomarker for pancreatic ductal adenocarcinoma (PDAC); however, tissue-based experiments have not been conducted. The aim of this study was to determine the tissue expression of AHNAK2 and to find the correlation between AHNAK2 and overall survival rate in PDAC. Results: AHNAK2 is highly expressed in PDAC (n=79) compared with adjacent normal tissues (n=64, P<0.001). Overexpression of AHNAK2 showed a significant relationship with a lower overall survival rate (P=0.033) in PDAC patients. The predictive value of increased expression of AHNAK2 remains relevant in patients with AJCC grade above II (n=43, P=0.006) or lymph node metastasis (n=32, P=0.004). Cox regression analysis showed that AHNAK2 expression (P=0.003) and pathology grade (P<0.001) are independent prognostic factors for PDAC. The nomogram model was performed to predict the 1- and 3-year survival rates based on Cox regression. The C-index was 0.61. The calibration curves were also made to show the association between the observed and predicted probability of the overall survival rates. Materials and Methods: AHNAK2 expression was performed in tissue microarrays by immunohistochemistry. The overall survival rate analysis was performed using the Kaplan-Meier method, Cox proportional hazards regression, and a nomogram model. Conclusions: AHNAK2 is overexpressed in PDAC tissues and is an independent prognostic factor in patients with PDAC.