Receptor for activated C kinase 1 (RACK1) is associated with certain aspects of cancer biology and signaling pathways, but its function in pancreatic ductal adenocarcinoma (PDAC) remains unknown. In the present study, 157 patients with PDAC were enrolled. RACK1 mRNA and protein expression levels were analyzed in PDAC tissues and matched adjacent noncancerous tissues by reverse transcription-quantitative polymerase chain reaction and western blotting. RACK1 expression levels in paraffin-embedded PDAC tissues were determined by immunohistochemistry. The associations between RACK1 expression and clinical data were evaluated using χ2 analysis. The relationship between RACK1 expression and the survival data of patients was analyzed using Kaplan-Meier and log rank tests. RACK1 mRNA and protein were revealed to be overexpressed in PDAC tumor tissues compared with adjacent noncancerous tissues. RACK1 expression was associated with clinical stage (P=0.001), lymph node invasion (P=0.003) and liver metastasis (P=0.001). Furthermore, patients with PDAC and high RACK1 expression demonstrated shorter overall survival times compared with patients with low RACK1 expression (P=0.002). Multivariate analysis indicated that RACK1 overexpression was an independent prognostic factor for patients with PDAC. Overexpression of RACK1 may contribute to tumor progression, and may be a potential prognostic biomarker for patients with PDAC.