Pancreatic cancer is known for its bad prognosis. Micro-RNAs mis-expressions are associated with various human cancers and offer new candidate targets for diagnostic and therapeutic strategies. Micro-RNA-222 has been shown to play a crucial role in cancer cell proliferation in recent studies. However, its correlations with the clinicopathological characters of pancreatic cancer still remain unclear. Through a prospective study of 60 pairs of pancreatic cancer tissues, adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between the expression of micro-RNA-222 and clinico-pathological characters was performed using the two-sample Student's t test. The survival correlations were analyzed by the Kaplan-Meier method and the Cox's proportional hazards model. Results showed that the expression levels of micro-RNA-222 were significantly elevated in the pancreatic cancer tissue compared with that in adjacent normal tissue. In addition, the overexpression of the tissue micro-RNA-222 strongly related to the expression level of Ki67. Finally, Cox's proportional hazards model analysis confirmed that micro-RNA-222 high expression level was an independent predictor of poor prognosis. This study provides the first evidence of a potential link between Ki67 and micro-RNA-222, which are both relevant to cell proliferation. Our data suggest the potential of micro-RNA-222 as a prognostic biomarker for the pancreatic cancer.