microRNA-218 (miR-218) is a vertebrate-specific miRNA that plays a crucial role in tumorigenesis and tumor progression. This study analyzed the miR-218 expression level and clinical significance in pancreatic cancer. One hundred and seven pairs of pancreatic cancer and adjacent normal tissues were analyzed by quantitative reverse-transcriptase polymerase chain reaction. The correlation between miR-218 expression and clinicopathological characters was determined by the two-sample Student t-test. The survival correlations were analyzed by the Kaplan-Meier method and Cox proportional hazards model. The relative expression of miR-218 in pancreatic cancer tissues (2.63 ± 1.59) was significantly lower than that in matched noncancerous pancreatic tissues (6.52 ± 2.50, P < 0.001). The low expression of miR-218 in the pancreatic cancer tissues were strongly correlated with the TNM classification (P = 0.02), distant metastasis (P = 0.001), and tumor differentiation (P = 0.003). The low level of miR-218 expression was significantly correlated with the shorter overall survival time of pancreatic cancer patients (5-year overall survival rate: 7.5 vs 34.9%; log-rank test: P < 0.001). Multivariate analyses confirmed that a low level of miR-218 expression was an independent predictor of poor prognosis in pancreatic cancer patients (Hazard ratio: 7.24; 95% confidence interval: 2.01-18.28; P = 0.007). Our findings suggested a significant downregulation in the expression of miR-218; this might have considerable potential value in the prognosis for pancreatic cancer.