Human pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with early metastasis, which leads to poor prognosis for patients. Mounting evidence suggests that microRNAs (miRNAs) act as critical factors for tumor recurrence and metastasis. miR-153 has been suggested as a novel tumor-associated miRNA, which is involved in tumor metastasis. However, the clinical significance of miR-153 and its role in PDAC remains to be investigated. The aim of the present study was to investigate the expression levels of miR-153 using RT-qPCR in human PDAC cell lines and tissues. A clinical association analysis was performed to investigate the clinical significance of miR-153. The results showed that, the relative expression of miR-153 in PDAC cells was obviously decreased as compared to that in the normal human pancreatic duct epithelial cell line. The mean expression of miR-153 in PDAC tissues was significantly reduced as compared to that in the normal pancreatic tissues. The clinical analysis revealed that a low expression of miR-153 was closely associated with poor prognostic features and shorter long-term survival of PDAC patients. Furthermore, univariate and multivariate Cox regression analyses showed that miR-153 was an independent prognostic factor for predicting survival in PDAC patients. In vitro studies demonstrated that the upregulation of miR-153 inhibited migration and invasion in MIAPaCa-2 cells. By contrast, the downregulation of miR-153 increased the number of migrated and invaded AsPC-1 cells. miR-153 inversely regulated SNAI1 abundance in MIAPaCa-2 cells. Notably, SNAI1 was identified as a direct target of miR-153 in PDAC. Furthermore, an inverse correlation between miR-153 and SNAI1 expression was observed in PDAC tissues. In conclusion, the results showed miR-153 is an independent prognostic marker for predicting survival in PDAC patients and inhibits cell migration and invasion by targeting SNAI1.